Method for implanting a stimulator with a foil-like electrode portion

ABSTRACT

By being implanted deeper and/or more accurately, comfort and/or reliability for the subject may be improved. In addition, the chance that the stimulator is implanted under the nerve tissue is greatly increased.

FIELD OF THE DISCLOSURE

The present application relates generally to methods for implanting amedical device, more particularly an implantable stimulator with afoil-like portion. The implantable stimulator may have a foil-likesubstrate, and be configured and arranged for providing electricalstimulation to human or animal tissue. In particular, the implantablestimulator may have a conformable foil-like portion comprising at leasttwo electrodes. This application also relates to methods for implantingan implantable stimulator under nerve tissue of a subject.

BACKGROUND

The present application relates to the field of implantable electricalstimulation systems, which may be used to deliver electrical stimulationtherapy to subjects to treat a variety of symptoms or conditions such asheadaches, lower back pain and incontinence. In many electricalstimulation applications, it is desirable for a stimulator, typicallycomprising a therapeutic lead (a lead comprises electrodes andelectrical wire connections), to provide electrical stimulation to oneor more precise locations within a body.

Such systems and devices may be implanted for improving headachedisorders, chronic pain of peripheral origin or other disorder in asubject suffering therefrom by electrically modulating neural tissue.

In general, implantation includes subcutaneous or percutaneous placementof at least the electrodes of the neurostimulation system or device. Oneor more elements of the device may remain located external to be body,being connected wirelessly and/or wired to the rest of the system ordevice. Preferred are minimally invasive implantation procedures,systems and devices that can reliably operate for extended periods, andsystems and devices providing a high degree of comfort for the subject.Incorrect placement may create unexpected and/or unpredictableelectrical resistance between one or more electrodes and the underlyingtissue. Subcutaneous placement, particularly in bodily regions where theskin is relatively thin, such as the cranium, may affect subjectcomfort, and can cause irritation of the overlying skin.

The specialist performing the implantation may need to address practicalissues which can reduce the degree of satisfaction with theimplantation, such as an adequate placement of the electrodes withrespect to the nerve tissue to be stimulated, and the availability ofone or more convenient locations for the electrode leads,interconnecting wires, any operating electronics/electrical componentsand any power supplies.

SUMMARY

It is to be understood that both the following summary and the detaileddescription are exemplary and explanatory and are intended to providefurther explanation of the invention as claimed. Neither the summary northe description that follows is intended to define or limit the scope ofthe invention to the particular features mentioned in the summary or inthe description. Rather, the scope of the invention is defined by theappended claims

In certain embodiments, the disclosed embodiments may include one ormore of the features described herein.

Products and methods described herein provide methods to implantstimulators that are not symmetrically dimensioned. Additionally, theymay be advantageously used with stimulators having a relatively highdegree of conformability, which may increase the comfort for thesubject. Improved implantation procedures disclosed herein arerepeatable and reproducible for a wide range of subjects, whileproviding a high degree of satisfaction for the subjects

A method is provided for implanting an implantable stimulator undernerve tissue of a subject, the implantable stimulator comprising: asubstrate, comprising a first surface and a second surface, wherein athickness of the substrate is defined by the first and second surfaces;and at least two electrodes located along a conformable first portion ofthe substrate, the thickness of the substrate along the conformablefirst portion being equal to or less than 0.5 millimeters; the methodcomprising: identifying a target location for stimulation which intransverse cross-section comprises an outer skin layer, nerve tissue tobe stimulated, and an inner aponeurosis layer; forming one or moreincisions proximate the target location; introducing the conformablefirst portion in the skin layers at the target location, whereby the atleast two electrodes are disposed under the nerve tissue to bestimulated and above or in the inner aponeurosis layer.

It may be advantageous to introduce the first portion such that the atleast two electrodes are disposed in skin layers above or in aponeurosislayer. There are typically fewer blood vessels, so the risk of damage toother anatomical structures may be reduced. In addition, implantation“under” the nerve tissue is simplified for the specialist—in thiscontext, “under” the nerve means a skin depth location between the nervetissue and the underlying bone tissue. By using a first portion with agreatly reduced thickness, such as 0.5 mm or less, introduction deeperunder the skin becomes possible. Additionally or alternatively, comfortfor the subject may be improved if the stimulator is located deeperunder the skin. By using a conformable first portion, insertion may bemade more precisely at the interfaces between skin layers—the risk maybe reduced of tissue damage during insertion, and the conformable firstportion may more easily follow anatomical curvature. Also, by selectinglocations where aponeurosis tissue is present, the risk that muscletissue is disposed between the stimulator and the nerve tissue to bestimulated is greatly reduced.

An implantation method is provided, wherein the method comprises:introducing the conformable first portion, whereby the at least twoelectrodes are disposed in the skin layers between subcutaneous fat andthe aponeurosis layer. Additionally or alternatively, the methodcomprises: introducing the first portion, whereby the at least twoelectrodes are disposed in the skin layers directly adjacent to theaponeurosis layer. Additionally or alternatively, the method comprises:removing one or more skin layers, including an outer skin layer andsubcutaneous fat, before introducing the first portion.

Deeper locations within the skin further increase the chance that thefirst portion is introduced below the nerve. Comfort for the subject mayalso be improved if the stimulator is located deeper under the skin.Additionally or alternatively, it is relatively straightforward for aspecialist to identify the transition between the subcutaneous fat layerand the underlying tissue.

An implantation method is provided, wherein the method comprises:forming an incision proximate an implantation location; and introducinga further portion of the substrate in the skin layers, whereby thefurther portion is disposed between subcutaneous fat and above or inmuscle tissue.

This may allow a more complete implantation of the implantablestimulator, which may reduce infection risk, and may increase thepositional stability of the first portion.

Additionally or alternatively, the method comprises: introducing thefurther portion, whereby the further portion is disposed in the skinlayers between subcutaneous fat and a bone layer. Additionally oralternatively, the method comprises: introducing the further portion,whereby the further portion is disposed in the skin layers directlyadjacent to the muscle tissue. Additionally or alternatively, the methodcomprises: removing one or more skin layers, including an outer skinlayer and subcutaneous fat, before introducing the further portion.

By implanting deep or below subcutaneous fat, comfort may be improvedfor the subject as the further portion is covered by more skin layers.It may also be advantageous for the specialist to implant the firstportion and further portion at approximately the same depth in the skin.

The methods described may be used to reliably implant below nerve tissueto be stimulated. Additionally, the methods described using one or moreintroducer sheaths may be used to further improve the under-nerveimplantation methods.

Additionally or alternatively, the substrate is longitudinally-extended,further comprising a further portion; the first portion has a firstmaximum transverse cross-section and the further portion has a furthermaximum transverse cross-section, the further maximum transversecross-section being at least 1.2 times greater than the first maximumtransverse cross-section; the method comprising: forming a first andsecond incision on opposite sides of the target location; introducing afirst introducer sheath under the skin from the second incision to thefirst incision, the first introducer sheath having a maximum internaltransverse cross-section less than the further maximum transversecross-section of the substrate; introducing the conformable firstportion, comprising the at least two electrodes, into the firstintroducer sheath from the first incision to the second incision;removing the first introducer sheath, whereby the implantable stimulatorextends under the skin from the further portion at the first incision tothe conformable first portion at the second incision, whereby the atleast two electrodes are arranged to transfer treatment energy to thetarget location.

By using a first introducer with a minimum internal transversecross-section greater than the maximum cross-section of the firstportion, the first portion may be introduced into the first introducer.It is not necessary to introduce the further portion, so the maximuminternal transverse cross-section of the first introducer may besignificantly less than the maximum transverse cross-section of thefurther portion of the stimulator. Using an introducer sheath and twoincisions, the stimulator may be implanted at many target locations ofthe subject. This may be even more advantageous if the first portion isconformable.

Additionally or alternatively, the method comprises: forming a thirdincision between the first and second incisions; introducing the firstintroducer sheath under the skin from the second incision to the thirdincision instead of from the second incision to the first incision;introducing a second introducer sheath under the skin from the thirdincision to the first incision, the second introducer sheath having amaximum internal transverse cross-section less than the further maximumtransverse cross-section of the substrate; introducing the first portionof the implantable stimulator, comprising the at least two electrodes,into the second introducer sheath from the first incision to the thirdincision position; removing the second introducer sheath; introducingthe first portion of the implantable stimulator, comprising the at leasttwo electrodes, into the first introducer sheath from the third incisionto the second incision; and removing the first introducer sheath,whereby the implantable stimulator extends under the skin from thefurther portion at the first incision to the first portion at the secondincision.

Using a first and second introducer sheaths and three incisions, thestimulator may be implanted at many target locations in the body of thesubject where the first portion and the further portion are to beseparated by at least one portion of curved skin. This may be even moreadvantageous if the first portion is conformable

A method is provided for implanting an implantable stimulator, theimplantable stimulator comprising: a longitudinally-extended substratehaving a conformable first portion and a further portion; at least twoelectrodes, comprised in the conformable first portion; wherein thefirst portion has a first maximum transverse cross-section and thefurther portion has a further maximum transverse cross-section, thefurther maximum transverse cross-section being at least 1.2 timesgreater than the first maximum transverse cross-section; the methodcomprising: identifying a target location of a subject for stimulation;forming a first and second incision on opposite sides of the targetlocation; introducing a first introducer sheath under the skin from thesecond incision to the first incision, the first introducer sheathhaving a maximum internal transverse cross-section less than the furthermaximum transverse cross-section of the substrate; introducing theconformable first portion, comprising the at least two electrodes, intothe first introducer sheath from the first incision to the secondincision; removing the first introducer sheath, whereby the implantablestimulator extends under the skin from the further portion at the firstincision to the conformable first portion at the second incision wherebythe at least two electrodes are arranged to transfer treatment energy tothe target location.

By using a first introducer with a minimum internal transversecross-section greater than the maximum cross-section of the firstportion, the first portion may be introduced into the first introducer.It is not necessary to introduce the further portion, so the maximuminternal transverse cross-section of the first introducer may besignificantly less than the maximum transverse cross-section of thefurther portion of the stimulator. Using an introducer sheath and twoincisions, the stimulator may be implanted at many target locations ofthe subject. This may be even more advantageous if the first portion isconformable.

Additionally or alternatively, the method comprises: introducing a guidewire under the skin between the first and second incisions, the guidewire having a maximum transverse cross-section less than the minimuminternal transverse cross-section of the introducer sheath; introducingthe first introducer sheath over the guide wire under the skin from thesecond incision to the first incision; and removing the guidewire,whereby the first introducer sheath extends under the skin from thesecond incision to the first incision.

By using a guide wire dimensioned to accept the first introducer, it mayspeed up the procedure. Additionally or alternatively, it may reduceunwanted tissue damage during insertion of the first introducer.Additionally or alternatively, it may allow a smaller dimensionedintroducer to be used as it does not need to be as rigid.

Additionally or alternatively, the method comprises: inserting the tipof an guidewire introducer needle into the first incision and furtherinserting the guidewire introducer needle under the skin until the tipemerges from the second incision, the guidewire introducer needle havinga minimum internal transverse cross-section greater than the maximumtransverse cross-section of the guide wire; inserting the guide wirethrough the guidewire introducer needle; and removing the guidewireintroducer needle from under the skin to leave the guide wire extendingunder the skin through the first incision to the second incision.

By using a guidewire introducer needle dimensioned to accept the guidewire, it may further speed up the procedure. Additionally oralternatively, it may reduce unwanted tissue damage during insertion ofthe guide wire. Additionally or alternatively, it may allow a smallerdimensioned guide wire to be used as it does not need to be as rigid.

Additionally or alternatively, the method comprises: forming a skinpocket around the first incision, arranged to accept the further portionof the implantable stimulator; and introducing the further portion ofthe implantable stimulator into the skin pocket at the first incision.

Conventionally, implants are implanted just under the outer layer ofskin. However, by implanting deep or below subcutaneous fat, comfort maybe improved for the subject as the further portion is covered by moreskin layers. It may also be advantageous for the specialist to implantthe first portion and further portion at approximately the same depth inthe skin.

Additionally or alternatively, the method comprises: implanting at atarget location is under nerve tissue of the subject.

It is advantageous to implant the stimulator with one or more electrodesunder the nerve to be stimulated. By being implanted deeper, comfort forthe subject may be improved. In addition, if it the chance that thestimulator is implanted under the nerve tissue is relatively high, itmay allow a first portion with electrodes on only one surface (eitherthe first or second surface) to be more reliably used.

Additionally or alternatively, the substrate comprises a first andsecond surface defining a thickness of the substrate, the thickness ofthe substrate along the conformable first portion being 0.5 millimeteror less.

By using a first portion with a greatly reduced thickness, such as 0.5mm or less, introduction deeper under the skin becomes possible.Additionally or alternatively, comfort for the subject may be improvedif the stimulator is located deeper under the skin. By using aconformable first portion, insertion may be made more precisely at theinterfaces between skin layers—the risk may be reduced of tissue damageduring insertion, and the conformable first portion may more easilyfollow anatomical curvature.

Additionally or alternatively, the method comprises: forming a thirdincision between the first and second incisions; introducing the firstintroducer sheath under the skin from the second incision to the thirdincision instead of from the second incision to the first incision;introducing a second introducer sheath under the skin from the thirdincision to the first incision, the second introducer sheath having amaximum internal transverse cross-section less than the further maximumtransverse cross-section of the substrate; introducing the first portionof the implantable stimulator, comprising the at least two electrodes,into the second introducer sheath from the first incision to the thirdincision position; removing the second introducer sheath; introducingthe first portion of the implantable stimulator, comprising the at leasttwo electrodes, into the first introducer sheath from the third incisionto the second incision; and removing the first introducer sheath,whereby the implantable stimulator extends under the skin from thefurther portion at the first incision to the first portion at the secondincision.

By using a first and second introducer with a minimum internaltransverse cross-section greater than the maximum cross-section of thefirst portion, the first portion may be introduced into the first andsecond introducer. It is not necessary to introduce the further portion,so the maximum internal transverse cross-section of the first introducermay be significantly less than the maximum transverse cross-section ofthe further portion of the stimulator. Using a first and secondintroducer sheaths and three incisions, the stimulator may be implantedat many target locations in the body of the subject where the firstportion and the further portion are to be separated by at least oneportion of curved skin. This may be even more advantageous if the firstportion is conformable.

The methods described using one or more introducer sheaths may be usedto reliably position a stimulation device at an implantation sitesufficiently close to the nerve to be stimulated. Additionally, themethods described for reliably implanting under the nerve may be used tofurther improve the introducer sheath methods.

Additionally or alternatively, wherein the target location identifiedfor stimulation comprises, in transverse cross-section, an outer skinlayer, nerve tissue to be stimulated, and an inner aponeurosis layer;the method comprises: introducing the conformable first portion in theskin layers at the target location, whereby the at least two electrodesare disposed under the nerve tissue to be stimulated and above or in theaponeurosis layer.

It may be advantageous to implant above or in aponeurosis layer. Thereare typically fewer blood vessels, so the risk of damage to otheranatomical structures may be reduced.

For performing the implantation using the one or more introducers, a kitof parts is advantageously provided comprising: a stimulator comprising:a longitudinally-extended substrate having a conformable first portionand a further portion; at least two electrodes, comprised in theconformable first portion; wherein the first portion has a first maximumtransverse cross-section and the further portion has a further maximumtransverse cross-section, the further maximum transverse cross-sectionbeing at least 1.2 times greater than the first maximum transversecross-section; a first introducer sheath having a maximum internaltransverse cross-section less than the further maximum transversecross-section of the substrate; a guide wire having a maximum transversecross-section less than the minimum internal transverse cross-section ofthe introducer sheath; and a guidewire introducer needle having aminimum internal transverse cross-section greater than the maximumtransverse cross-section of the guide wire.

Additionally the kit of parts may further comprise: a second introducersheath having: a maximum internal transverse cross-section less than thefurther maximum transverse cross-section of the substrate; and a minimuminternal transverse cross-section greater than the maximum transversecross-section of the guide wire.

Stimulators implanted according to the methods described in thisapplication may be advantageously used for stimulating: one or morenerves, one or more muscles, one or more organs, spinal cord tissue,brain tissue, one or more cortical surface regions, one or more sulci,and any combination thereof.

Stimulators implanted according to the methods described in thisapplication may be advantageously used for treatment of: headaches,primary headaches, incontinence, occipital neuralgia, sleep apnea,hypertension, gastro-esophageal reflux disease, an inflammatory disease,limb pain, leg pain, back pain, lower back pain, phantom pain, chronicpain, epilepsy, an overactive bladder, poststroke pain, obesity, anautoimmune disorder, rheumatoid arthritis, inflammatory bowel disease,Crohn's disease, and any combination thereof.

These and further and other objects and features of the invention areapparent in the disclosure, which includes the above and ongoing writtenspecification, with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and form a partof the specification, illustrate exemplary embodiments and, togetherwith the description, further serve to enable a person skilled in thepertinent art to make and use these embodiments and others that will beapparent to those skilled in the art. The invention will be moreparticularly described in conjunction with the following drawingswherein:

FIGS. 1A, 1B, 1C, 1D and 1E depict examples of an implantablestimulator;

FIG. 2A depicts a transverse cross-section through the head of a subjectin the target region for occipital nerve stimulation;

FIG. 2B depicts a transverse cross-section through the head of a subjectin the target region for supraorbital nerve stimulation;

FIG. 2C depicts a transverse cross-section through the head of a subjectin a convenient region for the further portion to be implanted;

FIG. 3A to 3V depict a method to implant a stimulator, suitable forsupraorbital nerve stimulation (SONS);

FIGS. 4A, 4B and 4C depict alternative electrode configurations suitablefor being comprised in an implantable stimulator;

FIG. 5 and FIG. 6 depict examples of nerves that may be stimulated totreat headaches;

FIG. 7 depicts examples of nerves that may be stimulated for othertreatments; and

FIG. 8A to 8O depict a method to implant a stimulator, suitable foroccipital nerve stimulation (ONS).

DETAILED DESCRIPTION

An implantable stimulator, and methods for implanting a stimulator willnow be disclosed in terms of various exemplary embodiments. Thisspecification discloses one or more embodiments that incorporatefeatures of the invention. The embodiment(s) described, and referencesin the specification to “one embodiment”, “an embodiment”, “an exampleembodiment”, etc., indicate that the embodiment(s) described may includea particular feature, structure, or characteristic. Such phrases are notnecessarily referring to the same embodiment. When a particular feature,structure, or characteristic is described in connection with anembodiment, persons skilled in the art may effect such feature,structure, or characteristic in connection with other embodimentswhether or not explicitly described.

In the several figures, like reference numerals may be used for likeelements having like functions even in different drawings. Theembodiments described, and their detailed construction and elements, aremerely provided to assist in a comprehensive understanding of theinvention. Thus, it is apparent that the present invention can becarried out in a variety of ways, and does not require any of thespecific features described herein. Also, well-known functions orconstructions are not described in detail since they would obscure theinvention with unnecessary detail. Any signal arrows in thedrawings/figures should be considered only as exemplary, and notlimiting, unless otherwise specifically noted.

The description is not to be taken in a limiting sense, but is mademerely for the purpose of illustrating the general principles of theinvention, since the scope of the invention is best defined by theappended claims.

It will be understood that, although the terms first, second, etc. maybe used herein to describe various elements, these elements should notbe limited by these terms. These terms are only used to distinguish oneelement from another. For example, a first element could be termed asecond element, and, similarly, a second element could be termed a firstelement, without departing from the scope of example embodiments. Asused herein, the term “and/or” includes any and all combinations of oneor more of the associated listed items. As used herein, “at least one ofA, B, and C” indicates A or B or C or any combination thereof. As usedherein, the singular form of a word includes the plural, and vice versa,unless the context clearly dictates otherwise. Thus, the references “a”,“an”, and “the” are generally inclusive of the plurals of the respectiveterms.

It should also be noted that in some alternative implementations, thefunctions/acts noted may occur out of the order noted in the figures.For example, two figures shown in succession may in fact be executedsubstantially concurrently or may sometimes be executed in the reverseorder, depending upon the functionality/acts involved.

As used herein, ranges are used herein in shorthand, so as to avoidhaving to list and describe each and every value within the range. Anyappropriate value within the range can be selected, where appropriate,as the upper value, lower value, or the terminus of the range.

The words “comprise”, “comprises”, and “comprising” are to beinterpreted inclusively rather than exclusively. Likewise the terms“include”, “including” and “or” should all be construed to be inclusive,unless such a construction is clearly prohibited from the context. Theterms “comprising” or “including” are intended to include embodimentsencompassed by the terms “consisting essentially of” and “consistingof”. Similarly, the term “consisting essentially of” is intended toinclude embodiments encompassed by the term “consisting of”. Althoughhaving distinct meanings, the terms “comprising”, “having”, “containing’and “consisting of” may be replaced with one another throughout thedescription of the invention.

“About” means a referenced numeric indication plus or minus 10% of thatreferenced numeric indication. For example, the term “about 4” wouldinclude a range of 3.6 to 4.4. All numbers expressing quantities ofingredients, reaction conditions, and so forth used in the specificationare to be understood as being modified in all instances by the term“about.” Accordingly, unless indicated to the contrary, the numericalparameters set forth herein are approximations that can vary dependingupon the desired properties sought to be obtained. At the very least,and not as an attempt to limit the application of the doctrine ofequivalents to the scope of any claims, each numerical parameter shouldbe construed in light of the number of significant digits and ordinaryrounding approaches.

Wherever the phrase “for example,” “such as,” “including” and the likeare used herein, the phrase “and without limitation” is understood tofollow unless explicitly stated otherwise.

“Typically” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where said event or circumstance occurs and instances where itdoes not.

FIGS. 1A, 1B & 1C depict longitudinal cross-sections through a firstembodiment 100 of an implantable stimulator comprising:

-   -   an electrode array 200, 400, comprised in a first portion 630,        with at least two electrodes 200, 400. Optionally, the first        portion 630 may be conformable.

In this example, one or more electrodes are provided of a first 200 a,200 b type and one or more electrodes of a second type 400 a, 400 b. Theelectrodes 200, 400 are comprised in the first 310 or second 320surface, and each is configurable for transferring treatment energy, inuse, to (as a stimulation electrode) and/or from (as a return electrode)human or animal tissue. In this context, an array may be considered asystematic arrangement of two or more electrodes 200 a, 200 b, 400 a,400 b. 1D, 2D or 3D arrays may be provided. Optionally, they may bearranged in rows and/or columns. In this example, the first portion 630comprises a 1D array with two electrodes of the first type 200 a, 200 band two electrodes of the second type 400 a, 400 b. However, asdescribed below, any number and type of electrodes may be used.

The implantable stimulator 100 further comprises:

-   -   a further portion 610 comprising one or more electrical and/or        electronic components. In this example, the further portion 610        comprises a pulse generator 500 (only depicted in FIGS. 1B and        1C), located along the further portion 610, for generating one        or more electrical treatment stimulation pulses. Additionally or        alternatively, the further portion 610 may comprise one or more        pulse energy receiver. The further portion 610 may also be        described as a proximal end; and    -   a substrate 300 extending longitudinally from the further        portion 610 to a first portion 630 along a longitudinal axis        600.

Optionally, the substrate (300) may comprise a conformable foil-likeportion, as explained below. Additionally or alternatively, thesubstrate 300 may comprise two or more adjacent polymeric substratelayers

The substrate 300 comprises a first 310 and second 320 surface, definingone or more thicknesses. Optionally, the surfaces may be substantiallyplanar. Additionally or alternatively, the pulse energy receiver orpulse generator may be comprised between the first and second surfaces.

The implantable stimulator 100 also comprises:

-   -   one or more electrical interconnections 250, between the further        portion 610 and the first 200 a, 200 b and the second 400 a, 400        b electrodes, for transferring electrical energy as one or more        electrical treatment stimulation pulses to the first electrode        200 a, 200 b and/or the second electrodes 400 a, 400 b. The one        or more electrical interconnections 250 are comprised between        the first surface 310 and the second 320 surfaces. In other        words, a plurality of electrical interconnections 250 are        comprised between the first 310 and second 320 surfaces using        metallization.

If the separation between the further portion 610 and the first portion630 is relatively large, a portion 350 of the substrate may be providedwhich comprises no stimulation electrodes. The length of this portion350 may be configured and arranged to allow the first portion 630 andthe further portion 610 to be located at different positions on and/orin the body.

In this disclosure, the conformability of the at least two electrodes200, 400 is determined to a high degree by the one or more of thefollowing:

-   -   the conformability of the substrate 300 proximate the electrodes        200, 400;    -   the arrangement and positions of the electrodes 200, 400;    -   the materials and dimensions (or extent) of the materials        comprised in the electrodes 200, 400;    -   the arrangement and positions of the one or more        interconnections 250 proximate the electrodes 200, 400; and    -   the materials and dimensions (or extent) of the materials        comprised in the interconnections 200, 400.

By suitable configuration, arrangement and optimization, an implantableportion with at least two electrodes 200, 400 may be provided which isfurther configured and arranged to be foil-like (or film-like) andhighly conformable.

As depicted, the substrate 300 is preferably elongated along thelongitudinal axis 600, having a tape-like shape, allowing the furtherportion 610 to be disposed further away from the position of theelectrodes 200, 400. This provides a high degree of flexibility if thedistal and further portions of the stimulator 100 have differenttransverse cross-sections.

If the substrate 300 is arranged substantially planar (for example, byallowing the substrate 300 to conform to a planar surface), the first310 and second 320 surfaces are disposed along substantially paralleltransverse planes 600, 700. As depicted in FIG. 1A and FIG. 1C, thefirst surface 310 lies in a plane comprising the longitudinal axis 600and a first transverse axis 700—the first transverse axis 700 issubstantially perpendicular to the longitudinal axis 600. As depicted inFIG. 1A, the plane of the first surface 310 is substantiallyperpendicular to the plane of the cross-section drawing (substantiallyperpendicular to the surface of the paper). As depicted in FIG. 1A andFIG. 1B, the second surface 320 lies in a plane comprising thelongitudinal axis 600 and the first transverse axis 700. As depicted inFIG. 1A, the plane of the first surface 310 is substantiallyperpendicular to the plane of the cross-section drawing (substantiallyperpendicular to the surface of the paper).

If the substrate 300 is conformable and foil-like, the substrate 300typically has a maximum thickness of 0.5 millimeter or less, proximatethe first 200 a, 200 b and second 400 a, 400 b electrodes.

As depicted, a thickness may be considered as a perpendicular distancebetween corresponding points on the first 310 and second surfaces 320.This is preferably determined when the substrate 300 conforms to aplanar surface.

As depicted in FIG. 1A, the substrate 300 thickness is an extent along asecond transverse axis 750—this second transverse axis 750 issubstantially perpendicular to both the longitudinal axis 600 and thefirst transverse axis 700—it lies in the plane of the drawing (along thesurface of the paper) as depicted. The first surface 310 is depicted asan upper surface and the second surface 320 is depicted as a lowersurface. The extent along the second transverse axis 750 (thickness) mayalso be described as a dimension of a cross-section in the transverseplane 700, 750.

The thickness may therefore be determined by a perpendicular distancealong the second transverse axis 750 between corresponding points on thefirst 310 and second surfaces 320.

The maximum thickness of a conformable and/or foil-like substrate 300along the first portion 630 is preferably 0.5 mm or less, preferably 0.3millimeters or less, even more preferably 0.2 millimeters or less, yetmore preferably 0.1 millimeters or less.

In general, the lower the maximum thickness (in other words, the thinnerthe substrate), the higher the degree of conformance.

Additionally or alternatively, the maximum thickness may be determinedproximate the first 200 a, 200 b and second 400 a, 400 b electrodes.

To clarify the differences between the different views depicted, theaxes are given nominal directions:

-   -   the longitudinal axis 600 extends from the further portion 610        (not depicted in FIG. 1A, but depicted in FIGS. 1B and 1C) on        the left, to the first portion 630, depicted on the right of the        page;    -   the first transverse axis 700 extends into the page as depicted        in FIG. 1A; and    -   the second transverse axis 750 extends from bottom to top as        depicted in FIG. 1A.

The substrate 300 may be configured and arranged as a multilayer,comprising two or more adjacent polymeric substrate layers having thefirst 310 and second 320 surface. The one or more electricalinterconnections 250 are also comprised between the first 310 and second320 surfaces. However, it is not necessary that the two or morepolymeric layers and/or interconnections have similar extents along thefirst transverse axis 700. In other words, within the context of thisdisclosure, there may be regions where an interconnection 250 issandwiched between regions of polymeric substrate (appears as amultilayer in a longitudinal cross-section), adjacent to regions wherethe polymeric substrate is substantially contiguous. Similarly, theremay be regions where an interconnection 250 is sandwiched between twopolymeric substrate layers (appears as a multilayer in a longitudinalcross-section), adjacent to regions where the substrate comprises twoadjacent substrate layers. Similarly, a substrate comprising two or morepolymeric substrate layer may be modified (physically and/orchemically), such that it appears to be one layer of polymericsubstrate.

These polymeric substrate layers are selected for suitability to beconformable, and to comprises the one or more electricalinterconnections 250. Preferably, the polymeric substrate materials arealso biocompatible and durable, such as a material selected from thegroup comprising silicone rubber, siloxane polymers,polydimethylsiloxanes, polyurethane, polyether urethane,polyetherurethane urea, polyesterurethane, polyamide, polycarbonate,polyester, polypropylene, polyethylene, polystyrene, polyvinyl chloride,polytetrafluoroethylene, polysulfone, cellulose acetate,polymethylmethacrylate, polyethylene, and polyvinylacetate. Suitableexamples of polymers, including LCP (Liquid Crystal Polymer) films, aredescribed in “Polymers for Neural Implants”, Hassler, Boretius,Stieglitz, Journal of Polymer Science: Part B Polymer Physics, 2011, 49,18-33 (DOI 10.1002/polb.22169), In particular, Table 1 is included hereas reference, depicting the properties of Polyimide (UBE U-Varnish-S),Parylene C (PCS Parylene C), PDMS (NuSil MED-1000), SU-8 (MicroChem SU-82000 & 3000 Series), and LCP (Vectra MT1300).

Conformable foil-like substrates 300 are configured to follow thecontours of the underlying anatomical features very closely by beingflexible. Very thin foil-like substrates 300 have the additionaladvantage that they have increased flexibility. In general, thinnerelements allow placement in a plurality of subcutaneous locations andprovide a higher degree of comfort to the subject.

Most preferably, the polymeric substrate layers comprise an LCP,Parylene and/or a Polyimide. LCP's are chemically and biologicallystable thermoplastic polymers which allow for hermetic sensor moduleshaving a small size and low moisture penetration.

Advantageously, an LCP may be thermoformed allowing complex shapes to beprovided. Very thin (and subsequently very conformable) and very flat(highly planar) layers of an LCP may be provided. For fine tuning ofshapes, a suitable laser may also be used for cutting.

For example, a conformable foil-like substrate 300 of LCP may have athickness (extent along the second transverse axis 750) in the range 50microns (um) to 720 microns (um), preferably 100 microns (um) to 300microns (um). For example, values of 150 um (micron), 100 um, 50 um, or25 um may be provided. The extent along the second transverse axis 750(thickness) may also be described as a dimension of a cross-section inthe transverse plane 700, 750.

When conforming to a substantially planar surface, the foil-like surface300 is substantially comprised in a plane with a transverse extentsubstantially perpendicular to the longitudinal axis 600, wherein theplanar width may be determined by a perpendicular distance betweencorresponding points on outer surfaces edges of the planar foil-likesubstrate 300 along the respective transverse extent. As depicted, thisis along the first transverse axis 700. Electrode 200, 400 widths of 2mm to 20 mm may be provided using LCP, for example. The extent along thefirst transverse axis 700 (width) may also be described as a dimensionof a cross-section in the transverse plane 700, 750

Typically, such a conformal foil-like substrates has an averagetransverse extent along the second transverse axis 750 (thickness) whichis equal to or less than the average transverse extent along the firsttransverse axis 700 (planar width).

At room temperature, thin LCP films have mechanical properties similarto steel. This is important as implantable substrates 300 should bestrong enough to be implanted, strong enough to be removed (explanted)and strong enough to follow any movement of the neighboring anatomicalfeatures and/or structures without deteriorating.

LCP belongs to the polymer materials with the lowest permeability forgases and water. LCP's can be bonded to themselves, allowing multilayerconstructions with a homogenous structure.

In contrast to LCP's, polyimides are thermoset polymers, which requireadhesives for the construction of multilayer portions with at least twoelectrodes. Polyimides are thermoset polymer material with hightemperature and flexural endurance.

An LCP may be used, for example, to provide conformable substrate 300 asa multilayer—in other words, two or more adjacent polymeric substratelayers. For example, these may be layers of 25 um (micron) thickness.

One or more electrical interconnections 250 may be provided between thefirst (310) and second (320) surfaces by metallization, for example.These may be conductors embedded in the substrate 300—for example, byhaving a single polymer layer and applying conductive material usingsuitable deposition techniques known from the semiconductor industry.For example, the substrate may comprise a first conformable layer and atleast one second conformable layer, wherein a plurality of electricalinterconnection layers 250 are positioned along the first layer using adeposition technique, and wherein the at least one second layer issecured to the first layer so as to cover the plurality of electricalinterconnections.

If two or more adjacent polymeric substrate layers are provided, aninterconnection layer may be provided using suitable techniques, forexample those from the semiconductor industry. The polymeric substratelayers may also be considered adjacent when one of more adhesion layersare used between them.

Lamination may also be used to provide a substrate 300 with the desiredphysical and chemical properties, and/or to provide a convenient methodof manufacture. For example, a substrate 300 may comprise threelaminated polymer layers: two high temperature thermoplastic layers witha low-temperature layer (bond-ply) in between, and high-temperaturelayers towards the first surface 310 and second surface 320.

In another example, two layers of silicone may be provided as polymericsubstrate layers: one layer of silicone is provided, metal is patternedon one of its outer surfaces, and a second layer of silicone is addedover the metal patterning by, for example, jetting, over-moulding, orspin-coating.

The electrical interconnections 250 may comprise one or more conductors,such as a metal, formed as required—for example, in one or moreconductive elements: wire, strand, foil, lamina, plate, and/or sheet.They may be a substantially contiguous (one conductor). They may alsocomprise more than one conductor, configured and arranged to be, in use,electrically connected with each other—in other words, the one or moreconductors are configured and arranged to be substantially electricallycontiguous in use.

Alternatively, the one or more electrical interconnections 250 may becomprised in one or more conductive interconnection layers 250, the oneor more conductive interconnection layers being comprised between twoadjacent polymeric substrate layers. As depicted in FIG. 1A, a pluralityof interconnections may be provided at different dispositions (ordepths) between the first surface 310 and the second surface 320.

An interconnection 250 in the context of this disclosure is notconfigured or arranged to be, in use, in contact with human or animaltissue. For example, by embedding the one or more interconnections 250in one or more layers of a low conductance or insulating polymer, suchas LCP. Additionally or alternatively, one or more encapsulation layersmay be used.

One or more interconnection layers 250 may also be provided bymetallization using techniques from the PCB (Printed Circuit Board)industry, such as metallization with a bio-compatible metal such as goldor platinum. Electro-plating may be used. Layers comprising LCP filmsare particularly suitable for metallization. These electricalinterconnections 250 and/or interconnect layers 250 are configured totransfer electrical energy as one or more electrical treatmentstimulation pulses from the pulse generator 500 to the first electrode200 a, 200 b and/or the second electrodes 400 a, 400 b.

Using suitable polymeric substrate materials, such as an LCP film,allows the conformable foil-like (or film-like) substrate 300 and the atleast two electrodes 200, 400 to have a high width-to-height ration,providing a bio-compatible electronic foil (or film), or bio-electronicfoil (or film).

For example, when the substrate 300 is arranged to conform to asubstantially planar surface, the ratio of maximum planar width 700 tomaximum thickness 750 proximate the first 200 a, 200 b and second 400 a,400 b electrodes may be 7:1 or higher, preferably 10:1 or higher, morepreferably 15:1 or higher, yet more preferably 30:1 or higher, even morepreferably 50:1 or higher.

Ratios of 100:1 or higher may also be advantageous, and may be providedusing one or more mechanically strong substrate layers of an LCP film,with a width of approximately 20 mm and a thickness of approximately 0.2mm. This provides a high degree of flexibility, and therefore also ahigh degree of conformability. Additional measures may also be taken toincrease the degree of conformability in the first transverse direction700, such as varying the width of the substrate, adding one or moreundulations and/or providing bending points.

When using a single row of electrodes 200, 400 and/or electrodes 200,400 with a smaller width, the width may be, for example, four mm with athickness of approximately 0.2 mm—this is a ratio of approximately 20:1.

Proximate the pulse generator 500, greater extents may be required whichfurther depend, to a high degree, on the dimensions of the electroniccomponents used, for example, a width of twenty mm and a thickness ofthree mm. This is a ratio of approximately 6.67:1.

As depicted in the example of FIG. 1A, the first portion 630 of thesubstrate 300 comprises:

-   -   two electrodes 200 a, 200 b of a first type, comprised in the        first surface 310, and    -   two electrodes 400 a, 400 b of a second type, also comprised in        the first surface 310. From proximal to first portion, the order        depicted is 200 a, 400 a, 200 b, 400 b—in other words, each        electrode of the first type 200 a, 200 b is proximate an        electrode of the second type 400 a, 400 b and comprised in the        same surface 310.

The substrate 300 comprises an electrical interconnection 250 betweeneach electrode 200 a, 400 a, 200 b, 400 b and the pulse generator. Inthis embodiment, each electrical interconnection 250 is configured andarranged such that each electrode 200 a, 400 a, 200 b, 400 b iselectrically connected substantially independently—consequently, one ofthe operating modes available by suitably configuring the pulsegenerator 500 is substantially independent operation. The pulsegenerator 500 may be configured using one or more hardware, firmwareand/or software parameters.

Although depicted in FIG. 1A as individual connections 250 at differentdistances between the first 310 and second 320 surfaces, the skilledperson will also realize that the same interconnections may be providedby a suitably configured interconnections 250 (or an interconnectionlayer 250) at approximately the same distance between the first 310 andsecond 320 surfaces.

“Comprised in” the first 310 or second 320 surface means that theelectrodes 200 a, 400 a, 200 b, 400 b are relatively thin (for example,if the substrate is arranged to conform to a substantially planarsurface, it may have an extent along the second transverse axis 750 of20 to 50 microns or less. Thinner electrodes may be also be used tofurther increase the degree of conformability, for example 1 micron orless), and attached to (or at least partially embedded in) the surface.

The electrodes 200, 400 may comprise a conductive material such as gold,platinum, platinum black, TiN, IrO2, iridium, and/or platinum/iridiumalloys and/or oxides. Conductive polymers, such as Pedot, may also beused. Preferably, bio-compatible conductive materials are used.PCB/metallization techniques may be used to manufacture them on or inthe first 310 and/or second 330 surfaces of the one or more polymericsubstrate layers.

Thicker metal layers are generally preferred over thinner metal layersfor electrodes 200 a, 200 b, 400 a, 400 b because they can be subjectedto bodily substances that may dissolve the metal. However, thicker metallayers typically increase rigidity (reduce conformability) proximate thethicker layer.

As depicted in FIG. 1, there is no substantial hardware differencebetween the first-type 200 a, 200 b and second type 400 a, 400 belectrodes—any difference in functionality is determined in this examplemainly by the configuration (one or more hardware, firmware and/orsoftware parameters) of the pulse generator 500. There may be a smallerinfluence on the electrical properties due to the arrangement androuting of the interconnections 250.

One or more electrodes of the same type 200 a, 200 b or 400 a, 400 b maybe operated substantially the same by suitable configuration of thepulse generator 500—in other words, the stimulation energy applied tothe electrodes 200, 400 is substantially the same at substantially thesame time instance (usually measured as a voltage, a current, a power, acharge, or any combination thereof). This may also be used to anticipateand/or correct for a misalignment and/or lead migration—this isadvantageous as it allows the configuration to be performed at leastpartially using software.

Additionally or alternatively, two or more electrodes 200, 400 may beconfigured and arranged using one or more parameters of the pulsegenerator 500 as a stimulation electrode or a return electrode. This mayprovide a higher degree of configurability as it only becomes necessaryto implant the substrate 300 such that at least two of the electrodesare proximate the desired stimulation location.

In this embodiment 100, the electrodes of the first type 200 a, 200 bare nominally configured and arranged to be operated as a stimulationelectrode.

The electrodes of the second type 400 a, 400 b are nominally configuredto be operated as a return electrode—each is configured to provide, inuse, an electrical return for one or more stimulation electrode 200 a,200 b. In other words, the electrical return 400 a, 400 b closes theelectrical circuit. It may also be similarly configured to provide anelectrical ground for a corresponding electrical energy source.

Three configurations are thus provided based on this nominalconfiguration: either:

-   -   a stimulation/return electrode pair 200 a/400 a proximate the        first surface 310 at that stimulation/return location; or    -   a stimulation/return electrode pair 200 b/400 b proximate the        first surface 310 at that stimulation/return location; or    -   a combination thereof.

In general, one or more stimulation electrodes 200 a, 200 b may beprovided in such a stimulator 100. The number, dimensions and/orspacings of the stimulating electrodes 200 a, 200 b may be selected andoptimized depending on the treatment—for example, if more than onestimulation electrode 200 a, 200 b is provided, each stimulationelectrode 200 a, 200 b may provide:

-   -   a different stimulation effect, a similar stimulation effect or        the same stimulation effect.

To avoid a misalignment, a selection may be made of one or twoelectrodes 200 a, 200 b proximate the tissues where the effect is to becreated.

Two or more stimulation electrodes 200 a, 200 b may be made active atsubstantially the same time if stimulation over a larger area isrequired and/or at a location between the active stimulation electrodes200 a, 200 b.

A stimulation electrode 200 a, 200 b may have, for example, dimensionsin the order of six to eight mm along the longitudinal axis 600, andthree to five mm along the first transverse axis 700, so approximately18 to 40 square mm (mm2).

A substrate 300, suitable for an implantable stimulator, may comprise,for example, up to twelve stimulation 200 a, 200 b and return 400 a, 400b electrodes over a length of 15 cm to allow for a correction formisalignment, or to simply allow the specialist to select the mosteffective stimulation location.

FIG. 1B depicts a view of the second surface 320 of the implantablefirst portion of the substrate 300 depicted in FIG. 1A. In other words,the second surface 320 is depicted in the plane of the paper, lyingalong the longitudinal axis 600 (depicted from bottom to top) and in thefirst transverse axis 700 (depicted from left to right). The secondtransverse axis 750 extends into the page. The first surface 310 is notdepicted in FIG. 1B, but lies at a higher position along the secondtransverse axis 750 (into the page), and is also substantially parallelto the plane of the drawing. The substrate 300 is arranged to conform toa substantially planar surface.

In general:

-   -   the first portion 630 comprises substantially only one or more        electrodes 200, 400 and one or more interconnections 250; and    -   the further portion 630 comprises one or more electrical        components, disposed between the second 320 surface and the        first 310 surface. Alternatively, the one or more electrical        components may be at least partially disposed on the first        surface 310 or on the second surface 320. Alternatively, the one        or more components may be at least partially embedded in the        first surface 310 or in the second surface 320.

Depending on, for example, the degree of embedding and the one or moreelectrical components used, the maximum thickness and/or planar widthmay be optimized. Components may be thinned to minimize the thickness.Components may include one or more pulse energy receivers and/or one ormore pulse generators 500 to provide, in use, stimulation pulses to theelectrodes 200, 400. Additional optional electrical components, such asan antenna (for example, a coil or dipole or fractal antenna), may alsoinfluence the thickness and/or width depending on the degree that theyare embedded in the substrate.

Advantageously, the further portion comprises a pulse generator 500.Optionally, it may be disposed between the second 320 surface and thefirst 310 surface. In FIGS. 1B and 1C, it is depicted with dotted lines.Alternatively, the pulse generator 500 may be at least partiallydisposed on the first surface 310 or on the second surface 320.Alternatively, the pulse generator 500 may be at least partiallyembedded in the first surface 310 or in the second surface 320.

Depending on, for example, the degree of embedding and the one or moreelectrical components used for the pulse generator 500, the maximumthickness (maximum transverse extent along the second transverse axis750) may be optimized. Additionally or alternatively, the maximum planarwidth (maximum transverse extent along the first transverse axis 700)may be optimized.

If the substrate 300 is configured and arranged to be conformable and/orfoil-like, the maximum thickness (extent along the second transverseaxis 750) of the implantable stimulator 100 proximate the pulsegenerator 500 may be five millimeters or less, preferably fourmillimeters or less, even more preferably three millimeters or less, thethickness being determined by a perpendicular distance betweencorresponding points on outer planar surfaces when the implantablestimulator 100 conforms to a substantially planar surface.

The maximum transverse extent 710 at the further portion 610 is arrangedoff-center with respect to the longitudinal axis 600. In this example,the proximal 630 end, the portion comprising no stimulation electrodes350 and the first portion 630 share a common boundary or edge along thefirst transverse axis. This may be more convenient to implant using theedge as a reference for positioning and/or creating an adequately sizedskin pocket. In addition, the orientation of the further portion 610 maybe used to determine upward and/or downward facing surface 310, 320.This may be advantageous where the electrodes 200, 400 are comprised inone surface 310, 320.

The stimulator 100 and the substrate 300 extend along the firsttransverse axis 700 (considered the planar width of the stimulator100/substrate 300 when conforming to a substantially planar surface). Asdepicted, the maximum planar width 710 at the proximate end 610 issubstantially greater than the maximum planar width 730 at the firstportion of the substrate 300. In this example, the maximum planar width710 proximate the pulse generator 500 is substantially greater than themaximum planar width 730 proximate the electrodes 200 a, 200 b, 400 a,400 b.

The maximum planar width 710 proximate the energy receivers and/or pulsegenerator 500 depends on, for example, the hardware and componentsused—typically, it is at least the width of the largest integratedcircuit used. Additional optional electrical components, such as anantenna (for example, a coil or dipole or fractal antenna), may alsoinfluence the maximum planar width.

The maximum planar width 730 proximate the electrodes 200 a, 200 b, 400a, 400 b depends on, for example, the conductors used for the electrodes200 a, 200 b, 400 a, 400 b and the one or more interconnections250—typically, it is at least the width of the first electrode 200 a,200 b or the second electrode 400 a, 400 b.

FIG. 1C depicts a view of the first surface 310 of the implantable firstportion of the substrate 300 depicted in FIGS. 1A and 1B. In otherwords, the first surface 310 is depicted in the plane of the paper,lying along the longitudinal axis 600 (depicted from bottom to top) andin the first transverse axis 700 (depicted from right to left). Thesecond transverse axis 750 extends out of the page. This is the viewfacing the animal or human tissue which is stimulated (in use). Thesecond surface 320 is not depicted in FIG. 1C, but lies at a lowerposition along the second transverse axis 750 (into the page), and isalso substantially parallel to the plane of the drawing. The substrate300 is arranged to conform to a substantially planar surface.

The one or more interconnections 250 are disposed between the first 310surface and the second 320 surface, as depicted in FIG. 1A. In FIG. 1C,they are depicted as dotted lines, representing the interconnections 250(or suitably configured one or more interconnection layers 250) thathave been provided for each of the electrodes 200 a, 200 b, 400 a, 400 bin this embodiment. A single dotted line 250 is depicted between thepulse generator 500 and the electrodes 200, 400 to indicate, in thisexample 100, that the interconnections 250 are at approximately the samedisposition along the first transverse axis 700.

As depicted in FIG. 1C, the electrodes 200 a, 200 b, 400 a, 400 b eachhave a longitudinal extent (length) along the longitudinal axis 600 anda transverse extent (width) along the first transverse axis 700.

Although depicted as similar, in practice, each electrode 200 a, 200 b,400 a, 400 b may vary in shape, transverse cross-section, orientationand/or size (or extent), depending on the intended use and/or thedesired degree of configurability.

After implantation of the stimulator 100, or at least of the conformablefirst portion comprising the at least two electrodes 200, 400, the pulsegenerator 500 may be configured and arranged to provide, in use,electrical energy to the one or more electrodes of the first type 200 a,200 b with respect to the electrical return applied to the one or moreelectrode of the second type 400 a, 400 b.

The configurability of the stimulator 100 allows, before, during and/orafter implantation of at least of the first portion comprising the atleast two electrodes 200, 400, the operation of the one or moreelectrodes 200 a, 200 b, 400 a, 400 b to be determined and/or adapted.The operation may also be reconfigured one or more times during theperiod that the stimulator 100 is implanted to optimize and/or prolongtreatment.

For example, the pulse generator 500 may be initially configured tonominally operate 200 a and 400 a as respectively a stimulation/returnelectrode pair. After implantation of at least the first portion 200,400, insufficient stimulation may be observed and/or measured. If it isassumed to be due to a mainly longitudinal misalignment, the pulsegenerator 500 may be alternatively configured, using one or moreparameters, to nominally operate 200 b and 400 b as respectively astimulation/return electrode pair.

The stimulator 100 may be further configured and arranged to switch thepulse generator 500 under predetermined and/or controlled conditionsbetween these configurations. It may be convenient to further considerthese configurations as a first and second electrode modes, and allow auser to select a mode as a preference and/or switch modes.Alternatively, the pulse generator 500 may switch modes underpredetermined and/or controlled conditions.

Additionally or alternatively, other modes may also be provided—forexample, configuring the pulse generator 500 to operate in:

-   -   a first electrode mode, wherein electrical stimulation energy is        provided to one or more electrodes of the first type 200 a, 200        b as one or more electrical treatment stimulation pulses, the        one or more electrodes of the second type 400 a, 400 b being        configured to provide, in use, a corresponding electrical return        for the one or more first electrodes 200 a, 200 b; or    -   a second electrode mode, wherein to one or more electrodes of        the second type 400 a, 400 b as one or more electrical treatment        stimulation pulses, the one or more electrodes of the first type        200 a, 200 b being configured to provide, in use, a        corresponding electrical return for the one or more second        electrodes 400 a, 400 b.

Again, the stimulator 100 may be further configured and arranged toswitch the pulse generator 500 under predetermined and/or controlledconditions between these configurations or modes. Additionally oralternatively, a user may be allowed to select a mode as a preferenceand/or switch modes.

The skilled person will realize that the electrodes 200 a, 200 b, 400 a,400 b may be configured to operate in more complex configurations, suchas:

-   -   400 a and 200 a may be operated as respectively a        stimulation/return electrode pair (reversing the original        intended operation);    -   400 b and 200 b may be operated as respectively a        stimulation/return electrode pair;    -   if an intermediate stimulation is preferred, two or more        electrodes 200 a, 200 b, 400 a, 400 b may be operated        substantially simultaneously as one or more stimulation        electrodes;    -   one or more electrodes 200 a, 200 b, 400 a, 400 b may be        operated as one or more return electrodes;    -   electrode 400 a operated as a stimulation electrode, in        combination with electrode 200 a and electrode 200 b as return        electrodes;    -   electrode 400 a and 200 b operated as a stimulation electrode,        in combination with electrode 200 a and electrode 400 b as a        return electrode.

Alternatively or additionally, the shape, orientation, transversecross-section, and/or size (or length) of one or more stimulationelectrodes may be differently configured compared to one or more returnelectrodes.

A number of parameters and properties may be considered when configuringand arranging the substrate 300 proximate the at least two electrodes200, 400 for conformability, such as:

-   -   the transverse 700 and/or longitudinal extent 600 of the one or        more electrodes 200 a, 200 b, 400 a, 400 b    -   the thickness of the substrate 300, or the perpendicular        distance between the first surface 310 and the second surface        320    -   the materials comprised in the substrate 300, and their physical        properties    -   the number and extent of interconnections 250 and/or        interconnection layers 250 between the first surface 310 and        second surface 320.

There have been attempts to make traditional leads, such as cylindricalleads, much thinner to allow subcutaneous implantation and/or toincrease comfort by flattening. But the surface area of the flattenedelectrodes may become disadvantageously small.

For example, a conventional 0.2 mm round lead with 1 cm long electrodesis estimated to result in an electrode with approximately 6 mm2electrode surface.

However, using the conformable first portions with at least twoelectrodes described herein, a relatively thin substrate 300 withdimensions of 0.2 mm thick, and four mm wide may be configured andarranged to provide approximately 35 mm2 electrode surface in the samelength. It is estimated that this may reduce impedance by a factor ofapproximately 35/6, and reduce power consumption by approximately 35/6.

FIG. 1D depicts a second embodiment of an implantable stimulator 101. Itis the same as the first embodiment 100 depicted in FIG. 1A to 1C,except:

-   -   the first portion 630 comprises a 1D array of eight electrodes        200, 400, which may be configured as one or more stimulation        electrodes 200 and one or more associated return electrodes 400;    -   the separation between the further portion 610 and the first        portion 630 is relatively small, so the portion of the substrate        comprising no stimulation electrodes is also relatively small;        and    -   the maximum transverse extent 710 at the further portion 610 is        arranged approximately centered with respect to the longitudinal        axis 600. This centered configuration may make it easier for the        specialist to use implantation tools and to estimate the        required extents for any skin pockets to be formed.

Alternatively or additionally, a short portion of the substratecomprising no stimulation electrodes may be manufactured longer, butshortened during the implantation—for example, by folding, twistingand/or implanting at least a portion of the surplus portion.

FIG. 1E depicts the third embodiment of an implantable stimulator 102.It is the same as the first embodiment 100 depicted in FIG. 1A to 1C,except:

-   -   the first portion 630 comprises a 1D array of twelve electrodes        200, 400, which may be configured as one or more stimulation        electrodes 200 and one or more associated return electrodes 400;    -   the separation between the further portion 610 and the first        portion 630 is visible and relatively large. So the portion of        the substrate comprising no stimulation electrodes 350 is also        relatively large; and    -   the maximum transverse extent 710 at the further portion 610 is        arranged approximately symmetrical with respect to the maximum        transverse extent 730 at the first portion 630. This may be more        convenient to manufacture.

Alternatively or additionally, the portion of the substrate comprisingno stimulation electrodes 350 may be provided by disabling and/ordisconnecting one or more electrodes 200, 400 in a portion with at leasttwo electrodes 630.

In general, stimulators 100 may be implanted by first creating asubcutaneous tunnel and/or using an implantation tool. However, a highdegree of conformability may make successful implantation moredifficult. Even when using a suitable insertion tool, the electrodepositions may be found later to be incorrect due to, for example,misalignment, lead migration during implantation, or lead migrationafter transplantation.

At least the first portion 630 comprising the at least two electrodes200, 400, is implanted. However, it may be advantageous to also implantthe further portion 610.

In addition, during implantation, it may be difficult to preciselyidentify the desired position for the stimulation—for example, thestimulator electrodes should be positioned sufficiently close to thenerve to be stimulated. But nerve pathways may not always be clearlyvisible to the specialist performing the implantation, and thedisposition and path of the nerve pathways vary greatly fromperson-to-person.

A further problem may occur when longitudinally-extended stimulatorshave relatively larger transverse extents (here described as thicknessor width)—the dimensions of implantation tools and/or subcutaneoustunnels are typically dimensioned based on the transverse extent. Thismeans that to implant stimulators with relatively larger transverseextents, larger dimensioned tools may be required and/or more invasiveprocedures may be required when using conventional methods.

In general, for any type of implantable stimulator with any type of leadand/or interconnection with any transverse cross-sectional shape, thetunnels and/or tools are dimensioned based on the largest transversecross-section of the portions of the stimulator to be implanted. If thefirst 700 and second 750 transverse axes are substantially perpendicularto the longitudinal axis 600, then it may also be defined as the maximumtransverse extent along one or more transverse axes 700, 750.

For stimulators with varying transverse cross-sections at positionsalong the longitudinal axis 600, the dimensions of implantation toolsand/or subcutaneous tunnels are typically dimensioned based on themaximum transverse cross-section at any point along the longitudinalaxis 600 of the implantable portion.

This may be particularly disadvantageous for stimulators where theinterconnecting wires cannot be disconnected from the further portionwithout a risk of damaging the encapsulation. As the stimulation sourcegenerally has a larger transverse cross-section, it is this transversecross-section which generally determines the minimum size of incisionsand/or implantation tools.

For the stimulators 100 disclosed herein, the maximum transversecross-section 710 of the further portion 610, is substantially greaterthan the maximum transverse cross-section 730 of the first portion 630.In this context, substantially greater means that the maximum proximaltransverse cross-section 710 is at least 20% greater than the maximumdistal transverse cross-section. In other words, greater by at least afactor of 1.2. In practice, stimulators may have factors greater than1.3, 1.5, 2.0, 3.0, 5.0, 10, as smaller first portions are oftenpreferred.

For example, maximum proximal transverse cross sections 710 may be inthe range 10 mm to 50 mm, such as 20 mm. For example, maximum distaltransverse cross sections 730 may be in the range 2 mm to 20 mm, such as4 mm

For such asymmetric stimulators, conventional implantation methods areless suitable.

Although in the examples disclosed herein, the maximum transversecross-sections 710, 730 are both along the first transverse axis 700, itwill be obvious to the skilled person that the methods may beadvantageously used where the maximum transverse cross-sections 710, 730may be along identical transverse axes, similar transverse axes, oralong substantially different transverse axes 700, 750.

FIG. 8A-8O depict a first method to implant a stimulator at a targetlocation, namely at approximately one cm superior (“above”) to theoccipital protuberance inion of a subject 1000. The disposition of theimplanted stimulator is suitable for occipital nerve stimulation (ONS).

This disclosure considers a first location 840 a and a second location840 b for a right occipital nerve stimulation and a first position 830 aand a second location 830 b for left occipital nerve stimulation—bothare depicted in FIG. 6 and described further below.

In human anatomy, the external occipital protuberance is located nearthe middle of the squamous part of occipital bone. The inion is thehighest point of this protuberance—it is commonly used as an anatomicallandmark—for example, in the 10-20 system in electroencephalography(EEG) recording.

Using this first method, the second embodiment of implantable stimulator101 depicted in FIG. 1D, may be advantageously implanted due to arelatively small portion 350 comprising no stimulation electrodes 200.

Additionally or alternatively, the portion of the substrate comprisingno stimulation electrodes comprised in the first 100 and thirdembodiments 102 may shortened during implantation to provide a suitablydimensioned stimulator. Advantageously, it may be shortened by thespecialist creating one or more additional skin pockets to retain excesslength of the substrate.

FIGS. 8A and 8B depict a recommended starting position from as viewedfrom above the subject 1000 and above the back 1015 of the subject'shead. The head of the subject is 1000 is placed face-down. A medianplane 800 of the subject 1000 is depicted vertically in FIGS. 8A and 8D,the arrow indicating the cranial direction. The median plane 800 is aplane of symmetry which divides the head of the subject 1000 into leftand right, passing through, for example, the spinal cord.

As depicted, the target area for stimulation is the second location 840b for a right occipital nerve stimulation and/or the second position 830b for left occipital nerve stimulation—the first portion 630 of theimplantable stimulator 101 is configured and arranged to stimulate oneor more regions on the back 1015 of the subject's 1000 head.

It may be advantageous to initially shave the region of skin beingtreated, including the area 1100 on the back 1015 of the head. In mostsubject's 1000, this position is covered with hair, which will furtherhide scarring and/or protruding portions which may occur afterimplantation.

FIG. 8C depicts an initial positioning of the implantable stimulator 101from above the back 1015 of the subject to determine the positions forthe incisions.

Through palpation and/or suitable scanning/imaging, the externaloccipital protuberance inion 1035 of the subject 1000 is located—this isto be used as the main anatomic landmark to help with positioning of thestimulator 101 for the first method.

The implantable stimulator 101 is positioned such that an approximatecenter of the first portion 630 electrodes array 200, 400 is positionedapprox. one cm 1220 superior (“above”) to the occipital protuberance1035 in the cranial direction along the median axis 800. Thelongitudinal length of the portion comprising at least two electrodes200, 400 extends laterally from the median plane 800, from the firstlateral border 1200 a to the second lateral border 1200 b.

For example, an eight cm long portion with at least two electrodes 200,400 may be used to provide approximately two laterally-disposed forty mmlengths of portions with at least two electrodes 200, 400 on each sideof the approximate center of the first portion 630. The longitudinalaxis 600 of the portion with at least two electrodes 200, 400 isdisposed approximately perpendicular to the median axis 800. The first1200 a and second 1200 b lateral borders are disposed approximatelyparallel to the median plane 800. In the case that electrodes 200, 400are comprised throughout the first portion 630, at the center point, thenumber of electrodes 200, 400 from the middle of the protuberance 1035are approximately equal.

The dimensions of the portion with at least two electrodes 200, 400 maybe predetermined and/or controlled to provide stimulation over asuitable area of tissue. For implantation at regions where anatomicvariation is relatively low for the expected subjects, it may beadvantageous to provide a stimulator with standardized dimensions.Additionally or alternatively, it may be advantageous to provide a rangeof standardized sizes and/or size ranges that the specialist may choosefrom. Additionally or alternatively, the stimulator may be configuredand arranged to be custom fit for one or more subjects. Additionally oralternatively, flexibility may be provided to the specialist by allowingone or more electrodes 200, 400 from a plurality of electrodes to beselected for the required stimulation.

Additionally or alternatively, it may be advantageous to use data fromone or more anatomical databases, such as DINED:https://dined.io.tudelft.nl/en/about to determine the most appropriatedimensions.

The stimulator 101 is flattened by the specialist over the outer surfaceof skin laterally from the median plane 800 to find the placement of thefurther portion 610 with either a pulse generator 500 or a pulse energyreceiver, such as a coil. As depicted, it is on the left side of thesubject's 1000 head. The longitudinal length of the further portion 610extends from the further lateral border 1210 a to the first lateralborder 1200 a/1210 b. The first 1200 a/1201 b and further 1210 a lateralborders are disposed approximately parallel to the median plane 800. Theimplantable stimulator 101 is preferably visually and/or manuallychecked to reduce the risk that the implantable stimulator substrate isstrained and/or twisted along its path—FIG. 8C.

It will be obvious to the skilled person that the method may be mirroredsuch that the further portion 610 is implanted on the right side of thesubject's 1000 head.

FIG. 8D depicts initial marking of the incision sites. The extent 1250of the further portion 610 is marked on the skin as a first incisionmark 1250 at the further lateral border 1210 a. A second 1260 incisionmark is marked on the skin to indicate the extent of the portion with atleast two electrodes 200, 400 (first portion 630) at the left lateralborder 1200 b. The first 1250 and second 1260 incision marks extendapproximately parallel to the median plane 800. For example, a tissuemarker 3000 may be used. It may also be advantageous to determine andmark the extent and positions of vascular structures (not depicted) inthis area—this may reduce the risk that the vascular structures aredamaged during the rest of the implantation method.

FIG. 8E depicts initial incisions. Two incisions are made using a tissueknife 3010, such as a surgical scalpel: the first at the first incisionmark 1250, approximately thirty mm in length; and the second at thesecond incision mark 1260, approximately twenty mm are made. The first1250 and second 1260 incisions extend approximately parallel to themedian plane 800.

FIG. 8F depicts the forming of skin pockets for receiving one or moreportions of the stimulator. Using a tissue knife 3010 and/or bluntscissors/forceps 3020, a second skin pocket is created extendingapproximately ten mm by, for example, blunt dissection around the second1260 incisions. Similarly, a first skin pocket is created, for example,by blunt dissection around the first incision 1250. As the maximumextent in transverse directions 700, 750 of the implantable stimulatorat the further portion 610 is greater than the maximum transverse extentof the first portion 630, the skin pocket at the first incision 1250 iscorrespondingly larger than at the second 1260 incision.

FIG. 8G depicts a possible preparation of the implant path. The tip of aguidewire introducer needle assembly 3030 a,b, preferably an epiduralneedle such as a Tuohy needle assembly, is inserted at the firstincision 1250 and further inserted under the skin until the tip emergesfrom the second incision 1260. The guidewire introducer mandrin 3030 bis removed from the guidewire introducer needle assembly 3030 a,b toleave the guidewire introducer needle 3030 a extending under the skinfrom the first incision 1250 to the second incision 1260. The guidewireintroducer needle 303 a is preferably blunt.

As depicted in FIG. 8H, a guide wire 3040 is inserted through theguidewire introducer needle 3030 a. The guidewire introducer needle 3030a is removed from under the skin to leave the guide wire 3040 extendingunder the skin from the first incision 1250 to the second incision 1260,extending on both sides from the incisions 1250, 1260.

As depicted in FIG. 8I, a first introducer assembly 3050 a,b is insertedunder the skin over the guidewire 3040 from the second incision 1260 tothe first incision 1250.

As depicted in FIG. 8J, the guide wire 3040 and first introducer mandrin3050 b are removed from under the skin to leave the first introducersheath 3050 a, extending under the skin through the second incision 1260to the first 1250 incision.

Alternatively, the first introducer assembly 3050 a,b may be insertedunder the skin over the guidewire 3040 from the first incision 1250 tothe second incision 1260. The guide wire 3040 and first introducermandrin 3050 b may be removed from under the skin to leave the firstintroducer sheath 3050 a, extending under the skin through the first1250 incision to the second incision 1260 position.

As depicted in FIGS. 8K and 8L, the first portion 630 of the implantablestimulator 101, comprising the portion with at least two electrodes 200,400, is inserted into the first introducer sheath 3050 a from the firstincision 1250 to the second incision 1260. The first portion 630 of theimplantable stimulator 101 is comprised within the body of the firstintroducer sheath 3050 a.

As depicted in FIGS. 8M and 8N, the first introducer sheath 3050 a isremoved. The first portion of the implantable stimulator 101 is pulledusing, for example, tweezers or silicone-tipped tweezers 3070, such thatit extends further from the second incision 1260 position, and thefurther portion of the implantable stimulator 101 with the electricalcomponents is introduced into the skin pocket at the first incision1250.

As depicted in FIG. 8O, the first portion of implantable stimulator 101is also pulled at the second incision 1260 using tweezers 3070 to checkthat the lead substrate is flattened underneath the skin—this may bechecked visually, using palpation and optionally with a diagnosticimager, such as an x-ray imager. If the portion with at least twoelectrodes 200, 400 positioning is incorrect, it may be corrected bygently pulling on the distal and/or further portion usingsilicone-tipped tweezers.

The tip of the first portion 630 is guided into the skin pocket at thesecond incision 1260. The first 1250 and second 1260 incisions areclosed, preferably in layers with subcutaneous and cutaneous sutures.

In this first method, the dimensions of implantation tools and/orsubcutaneous tunnels are typically dimensioned based on the maximumtransverse cross-section 700, 730, 750 of the first portion 630, and inparticular the portion with at least two electrodes 200, 400.

In other words, although the maximum proximal transverse cross-section710 is at least 1.2 times greater than the maximum distal transversecross-section 730, the further portion 610 dimensions do not directlyinfluence the dimensions of implantation tools and/or subcutaneoustunnels. However, the skilled person will realize that the first skinpocket created around the first incision 1250 should be dimensioned tobe sufficiently large enough for the further portion 610.

In this first method, the following implantation tools may be used:

-   -   a guidewire introducer needle assembly 3030 a,b, comprising a        guidewire introducer needle 3030 a enclosing a guidewire        introducer mandrin 3030 b (FIG. 8G). Preferably the guidewire        introducer needle 303 a is blunt. An epidural needle is        preferred—it is a hollow hypodermic needle, very slightly curved        at the end, suitable for inserting epidural catheters. A mandrin        is a stiff wire or tube used to give more flexible guidewire        introducer needles more resilience and strength when being        inserted and/or removed. Additionally or alternatively, a        mandrin may provide for closure of the lumen of the needle. The        lumen of the guidewire introducer needle 3030 a is at least        large enough to receive a suitable guide wire 3040—in other        words, the guidewire introducer needle 3030 a has a minimum        internal transverse cross-section which is greater than the        maximum transverse cross-section of the guide wire 3040; The        length is at least the distance from the first lateral border        1200 a to the second lateral border 1200 b. Typically, a gauge        of 20G is used. For example, a Tuohy needle assembly may be        used;    -   a guide wire 3040 is inserted through the guidewire introducer        needle 3030 a (FIG. 8H). The guidewire introducer needle 3030 a        is removed from under the skin to leave the guide wire 3040        extending under the skin. The maximum transverse cross-section        of the guide wire 3040 is at least sufficiently smaller than the        inner lumen dimensions of the guidewire introducer needle 3030 a        so that the guide wire 3040 may be inserted—in other words, the        guide wire 3040 has a maximum transverse cross-section less than        the minimum internal transverse cross-section of the guidewire        introducer needle 3030 a. The length is at least the distance        from the first lateral border 1200 a to the second lateral        border 1200 b. Typically, a gauge of 20G is used; and    -   a first introducer assembly 3050 a,b is inserted under the skin        over the guidewire 3040 (FIG. 8I). An introducer is generally an        instrument, such as a catheter, needle, or endotracheal tube,        for introduction of a flexible device. The first introducer        assembly 3050 a,b comprises a first introducer sheath 3050 a        enclosing a hollow first introducer mandrin 3050 b. The lumen of        the introducer mandrin 3050 b is at least large enough to        receive the guide wire 3040—in other words, the introducer        sheath 3050 a has a minimum internal transverse cross-section        that is greater than the maximum transverse cross-section of the        guide wire 3040. The length is at least the distance from the        first lateral border 1200 a to the second lateral border 1200 b.        Typically, a gauge of 20G is used. The lumen of the first        introducer sheath 3050 a is also at least large enough to        receive the first portion 630 of the implantable stimulator        101—in other words, the introducer sheath 3050 a has a minimum        internal transverse cross-section that is greater than the        maximum transverse cross-section of the first portion 630 of the        stimulator. The method is particularly advantageous when the        first introducer sheath 3050 a has a maximum internal transverse        cross-section less than the maximum proximal transverse        cross-section 710 of the substrate 300;

In summary, the method comprises at least the steps of:

-   -   identifying a target location for stimulation;    -   forming a first 1250 and second 1260 incision on opposite sides        of the target location;    -   introducing a first introducer sheath 3050 a under the skin from        the second incision 1260 to the first incision 1250, the first        introducer sheath 3050 a having a maximum internal transverse        cross-section less than the maximum proximal transverse        cross-section 710 of the substrate 300;    -   introducing the first portion 630 of the implantable stimulator        100, comprising the portion with at least two electrodes 200,        400, into the first introducer sheath 3050 a from the first        incision 1250 to the second incision 1260;    -   removing the first introducer sheath 3050 a, whereby the        implantable stimulator extends under the skin from the further        portion 610 at the first incision 1250 to the first portion 630        at the second incision 1260 whereby the at least two electrodes        200, 400 is arranged to transfer treatment energy to the target        location.

So, using an introducer sheath 3050 a and two incisions 1250, 1260, thestimulator 100, 101, 102, 103, 104, 105, may be implanted at many targetlocations in the body of the subject.

It may also be advantageous to implant the further portion 610 on theside of the subject's 1000 head, superior (“above”) to the ear 1020,1021. In that case, the first method may further comprise additionalacts, similar to the second method explained below, where a thirdincision is made to allow implantation of the further portion superiorto (“above”) the ear 1020, 1021. In that case, the first embodiment 100depicted in FIG. 1A to 1C, or the third embodiment of implantablestimulator 102 depicted in FIG. 1E, may be thus advantageously implanteddue to the portion 350 comprising no stimulation electrodes 200.

FIG. 3A-3V depict a second method to implant a stimulator, namely at atarget location of disposed midway on a subject's 1000 forehead 1010superior (“above”) to the right 1030 and left orbita 1031. Thedisposition of the implanted stimulator is suitable for supraorbitalnerve stimulation (SONS). It is similar to the first method describedabove in relation to FIG. 8A to 8O. The main differences are:

-   -   a further incision is used to implant along a curved portion of        skin; and    -   the incisions for the first portion are oriented along the        typical direction of wrinkles, which may reduce scarring.

Using this second method, the first embodiment 100 depicted in FIG. 1Ato 1C, or the third embodiment of implantable stimulator 102 depicted inFIG. 1E, may be advantageously implanted due to the portion 350comprising no stimulation electrodes 200. Additionally or alternatively,one or more electrodes 200, 400 in an array comprised in the secondembodiment 101 may be disconnected and/or disabled to form and/or extendthe portion 350.

FIGS. 3A and 3B depict a recommended starting position, viewedrespectively from above the subject 1000 and the right side of thesubject's 1000 head. The head of the subject is 1000 is placed in asupine position. A median plane 800 of the subject 1000 is depictedvertically in FIG. 3A, the arrow indicating the cranial direction.

As depicted, the target area for stimulation is a left supraorbitalnerve 810 and/or a right supraorbital nerve 820—the first portion 630 ofthe implantable stimulator 100, 102 is configured and arranged tostimulate one or more regions in the forehead 1010 between the orbita1030, 1031 and the dorsal side (top) of the skull.

It may be advantageous to initially shave the region of skin beingtreated, including the eyebrows (not indicated) and the areas 1100 oneach side of the head around the right ear 1020 for the further portion610—for example, see the highlighted area 1100 depicted in FIG. 3B. Itwill be obvious to the skilled person that the method may be mirroredsuch that the further portion 610 is implanted around the left ear 1021.

FIGS. 3C and 3D depict an initial positioning of the implantablestimulator 100, 102, viewed respectively from above the subject and theright side of the subject's 1000 head, to determine the positions forthe incisions.

Through palpation and/or suitable scanning/imaging, the lateral bordersof the orbita 1030, 1031, formed by the zygomatic bones, are used as themain anatomical landmarks to help position the stimulator 100, 102 forthe second method.

The implantable stimulator 100, 102 is positioned laterally, superior(“above”) to the left 1031 and right 1030 orbita, approximatelyperpendicular to the median plane 800, such that the first portion 630with electrodes 200, 400 is on the forehead 1010 directly above thetarget locations 810, 820. In this case, the portion with at least twoelectrodes 200, 400 extends 1200 at least from the lateral border 1200 aof the right orbita 1030 until the opposite lateral border 1200 b of theleft orbita 1031—FIG. 3C.

The dimensions of the portion with at least two electrodes 200, 400 maybe predetermined and/or controlled as discussed above for the firstmethod.

Additionally or alternatively, the data from specific studies may alsobe used, such as a Study of frontal hairline patterns for natural designand restoration; Sirinturk, Bagheri et al; Surgical and RadiologicAnatomy, vol 39, p. 679-684 (2017); DOI 10.1007/s00276-016-1771-1. Inthis study, they measured the average width of the forehead andspecifically the supraorbital region of 200 adults. The average width ofthe female supraorbital region was 125.3±13 5 mm, and of the malesupraorbital region was 133.9±15.9 mm.

The stimulator 100, 102 is flattened by the specialist over the outersurface of skin laterally from the median plane 800 to find theplacement of the further portion 610 with either a pulse generator 500or a pulse energy receiver, such as a coil. As depicted, it is on theright side of the subject's 1000 head superior (“above”) to the rightear 1020. The implantable stimulator 100, 102 is preferably visuallyand/or manually checked to reduce the risk that the implantablestimulator substrate is strained and/or twisted along its path—FIG. 3D.

It will be obvious to the skilled person that the method may be mirroredsuch that the further portion 610 is implanted on the left side of thesubject's 1000 head superior (“above”) to the left ear 1021.

FIG. 3E depicts initial marking of an incision site. The extent 1250 ofthe further portion 610 is marked on the skin as a first incision mark1250. The further portion 610 is to be implanted on the right-side ofthe subject 1000, superior (“above”) to the right ear 1020. The firstincision mark 1250 extends approximately parallel to the median plane800. For example, a tissue marker 3000 may be used. It may also beadvantageous to determine the extent and positions of vascularstructures 1040 in this area—this may reduce the risk that the vascularstructures 1040 are damaged during the rest of the implantation method.

FIG. 3F depicts further marking of the incision sites. A second 1260 andthird 1270 incision mark is marked on the skin along the longitudinalpath 600 of the portion with at least two electrodes 200, 400 portion ofthe implantable stimulator 100, 102 at respectively the lateral border1200 b of the left orbita 1031 and the lateral border 1200 a of theright orbita 1030. The second 1260 and third 1270 incision marks extendlaterally, which is approximately perpendicular to the median plane 800,in approximately the same direction as forehead wrinkles. This mayincrease comfort for the subject in some cases, and may reduce scarringin some cases.

Preferably, the second 1260 and third 1270 incision marks do not extendtoo far towards the median plane 800 because it may make the third 1270incisions more difficult to reach (as described below) when tunnelingfrom behind the ear towards the orbita with an guidewire introducerneedle across the orbita curve. Otherwise the subcutaneous trajectorymay need more force to reach the first portion 630.

FIG. 3G depicts initial incisions. Two incisions, each extendingapproximately twenty mm laterally, are made using a tissue knife 3010,such as a surgical scalpel. The second 1260 and third 1270 incisions areproximate the lateral borders respectively of each orbita 1031, 1030 andextend approximately perpendicular to the median plane 800.

FIG. 3H depicts a further incision. An incision, extending approximatelythirty mm, is made using a tissue knife 3010 at the first incision mark1250. The first 1250 incision depicted is on the right side of the head.The first incision 1250 extends longitudinally, approximately parallelto the median plane 800. Preferably vascular structures 1040 in thisarea are avoided.

FIG. 3I depicts the forming of skin pockets. Using a tissue knife 3010and/or blunt scissors/forceps 3020, two skin pockets are created on thefascia of approximately ten mm by, for example, blunt dissection aroundthe second 1260 and 1270 incisions.

Similarly (not depicted in FIG. 3I), a skin pocket is formed on thetemporal side by, for example, blunt dissection around the firstincision 1250. As the maximum transverse extent 700, 750 of theimplantable stimulator at the further portion 610 is greater than themaximum transverse extent 700, 750 at the first portion 630, the skinpocket at the first incision 1250 is similarly greater than at thesecond 1260 and third 1270 incisions.

FIG. 3J depicts a possible preparation of the implant path. The tip of aguidewire introducer needle assembly 3030 a,b, preferably as an epiduralneedle such as a Tuohy needle assembly, is inserted at the thirdincision 1270 and further inserted under the skin until the tip emergesfrom the second incision 1260. The guidewire introducer needle 3030 a,bis preferably blunt. The guidewire introducer mandrin 3030 b is removedfrom the guidewire introducer needle assembly 3030 a,b to leave theguidewire introducer needle 3030 a extending under the skin from thethird incision 1270 to the second incision 1260.

As depicted in FIG. 3K, a guide wire 3040 is inserted through theguidewire introducer needle 3030 a. The guidewire introducer needle 3030a is removed from under the skin to leave the guide wire 3040 extendingunder the skin from the third incision 1270 to the second incision 1260,extending on both sides from the incisions 1260, 1270.

As depicted in FIG. 3L, a first introducer assembly 3050 a,b is insertedunder the skin over the guidewire 3040 from the second incision 1260 tothe third incision 1270.

As depicted in FIG. 3M, the guide wire 3040 and first introducer mandrin3050 b are removed from under the skin to leave the first introducersheath 3050 a, extending under the skin through the second incision 1260to the third 1270 incision.

Alternatively, the first introducer assembly 3050 a,b may be insertedunder the skin over the guidewire 3040 from the third incision 1270 tothe second incision 1260. The guide wire 3040 and first introducermandrin 3050 b may be removed from under the skin to leave the firstintroducer sheath 3050 a, extending under the skin through the third1270 incision to the second incision 1260 position.

As depicted in FIG. 3N, the tip of the guidewire introducer needleassembly 3030 a,b is inserted at the first incision 1250 and furtherinserted under the skin until the tip emerges from the third incision1270. Due to the flexibility of guidewire introducer needles in general,it is expected that the same guidewire introducer needle assembly 3030a,b may be used as described above in relation to FIGS. 3J and 3K.However, it may be advantageous to provide a further guidewireintroducer needle assembly, configured and arranged to perform theseactions.

The guidewire introducer mandrin 3030 b is removed from the guidewireintroducer needle assembly 3030 a,b to leave the guidewire introducerneedle 3030 a extending under the skin from the first incision 1250 tothe third incision 1270.

As depicted in FIG. 3O, the guide wire 3040 is inserted throughguidewire introducer needle 3030 a. The guidewire introducer needle 3030a is removed from under the skin to leave the guide wire 3040 extendingunder the skin through the first incision 1250 to the third incision1270, extending on both sides from the incisions 1250, 1270. Due to theflexibility of guide wires in general, it is expected that the sameguide wire 3040 may be used as described above in relation to FIG. 3K.However, it may be advantageous to provide a further guide wire,configured and arranged to perform these actions.

As depicted in FIG. 3P, a second introducer assembly 3060 a,b isinserted under the skin over the guidewire 3040 from the third incision1270 to the first incision 1250. The second introducer 3060 a,b may beidentical, similar or different to the first introducer 3050 a,b. It maythe same type of introducer, but with identical, similar or differentdimensions.

As depicted in FIG. 3Q, the guide wire 3040 and second introducermandrin 3060 b are removed from under the skin to leave the secondintroducer sheath 3050 a, extending under the skin through the thirdincision 1270 to the first incision 1250.

Alternatively, the second introducer assembly 3060 a,b may be insertedunder the skin over the guidewire 3040 from the first incision 1250 tothe third incision 1270. The guide wire 3040 and second introducermandrin 3060 b may be removed from under the skin to leave the secondintroducer sheath 3060 a, extending under the skin through the first1250 incision to the third incision 1270 position.

As depicted in FIG. 3R, the first portion 630 of the implantablestimulator 100, 102, comprising the at least two electrodes 200, 400, isinserted into the second introducer sheath 3060 a from the firstincision 1250 to the third incision 1270. The first portion 630 of theimplantable stimulator 100, 102 extends from the third incision 1270position.

As depicted in FIG. 3S, the second introducer sheath 3060 a is removed.The first portion 630 of the implantable stimulator 100, 102 is pulled,using, for example, tweezers or silicone-tipped tweezers 3070, such thatit extends further from the third incision 1270 position, and thefurther portion 610 of the implantable stimulator 100, 102 with theelectrical components is introduced into the ipsilateral skin pocket atthe first incision 1250.

As depicted in FIG. 3T, the first portion 630 of the implantablestimulator 100, 102, comprising the portion with at least two electrodes200, 400, that extends from the third incision 1270 is threaded throughthe first introducer sheath 3050 a to the second incision 1260.

As depicted in FIG. 3U, the first introducer sheath 3050 a is removed.

As depicted in FIG. 3V, the first portion 630 of implantable stimulator100, 102 is pulled at the second incision 1260 using tweezers 3070. Itis advantageous to check that the lead substrate is flattened underneaththe skin—this may be checked visually, using palpation and optionallywith a diagnostic imager, such as an x-ray imager. If the portion withat least two electrodes 200, 400 is incorrectly positioned, it may becorrected by gently pulling on the distal 630 and/or further portion 610using silicone-tipped tweezers. Alternatively or additionally, thepositioning may be corrected by gently pulling at the substrate portionaccessible through the third incision 1270.

The tip of the first portion 630 is guided into the skin pocket at thesecond incision 1260. The first 1250, second 1260 and third 1270incisions are closed, preferably in layers with subcutaneous andcutaneous sutures.

In this second method, similar to the first method, the dimensions ofimplantation tools and/or subcutaneous tunnels are typically dimensionedbased on the maximum transverse cross-section 700, 730, 750 of the firstportion 630, and in particular the portion with at least two electrodes200, 400.

In this second method, the following implantation tools may be used:

-   -   a guidewire introducer needle assembly 3030 a,b, comprising a        guidewire introducer needle 3030 a enclosing a guidewire        introducer mandrin 3030 b (FIG. 3J). The lumen of the guidewire        introducer needle 3030 a is at least large enough to receive a        suitable guide wire 3040—in other words, the guidewire        introducer needle 3030 a has a minimum internal transverse        cross-section which is greater than the maximum transverse        cross-section of the guide wire 3040. The length is at least the        distance from the first lateral border 1200 a to the second        lateral border 1200 b. Typically, a gauge of 20G is used. For        example, an epidural needle such a Tuohy needle assembly may be        used. Preferably, the guidewire introducer needle is blunt;    -   a guide wire 3040 is inserted through the guidewire introducer        needle 3030 a (FIG. 3K). The guidewire introducer needle 3030 a        is removed from under the skin to leave the guide wire 3040        extending under the skin. The maximum transverse cross-section        of the guide wire 3040 is at least sufficiently smaller than the        inner lumen dimensions of the guidewire introducer needle 3030 a        so that the guide wire 3040 may be inserted—in other words, the        guide wire 3040 has a maximum transverse cross-section less than        the minimum internal transverse cross-section of the guidewire        introducer needle 3030 a. The length is at least the distance        from the first lateral border 1200 a to the second lateral        border 1200 b. Typically, a gauge of 20G may be used;    -   a first introducer assembly 3050 a,b is inserted under the skin        over the guidewire 3040 (FIG. 3L). The first introducer assembly        3050 a,b comprises a first introducer sheath 3050 a enclosing a        hollow first introducer mandrin 3050 b. The lumen of the        introducer mandrin 3050 b is at least large enough to receive        the guide wire 3040—in other words, the introducer sheath 3050 a        has a minimum internal transverse cross-section that is greater        than the maximum transverse cross-section of the guide wire        3040. The length is at least the distance from the first lateral        border 1200 a to the second lateral border 1200 b. Typically, a        gauge of 20G may be used. The lumen of the first introducer        sheath 3050 a is also at least large enough to receive the first        portion 630 of the implantable stimulator 100, 102—in other        words, the introducer sheath 3050 a has a minimum internal        transverse cross-section that is greater than the maximum        transverse cross-section of the first portion 630 of the        stimulator. The method is particularly advantageous when the        first introducer sheath 3050 a has a maximum internal transverse        cross-section less than the maximum proximal transverse        cross-section 710 of the substrate 300;    -   optionally, a further guidewire introducer needle assembly,        comprising a further guidewire introducer needle enclosing a        further guidewire introducer mandrin (FIG. 3N, FIG. 3O). The        lumen of the further guidewire introducer needle is at least        large enough to receive a further guide wire. The length is at        least the distance from the first incision 1250 to the third        incision 1270. Typically, a gauge of 20G is used. For example,        an epidural needle such as Tuohy needle assembly may be used.        Preferably, the further guidewire introducer needle is blunt.        Preferably, the same guidewire introducer needle assembly 3030        a,b is used as described above in relation to FIGS. 3J and 3K;    -   a further guide wire is inserted through the further guidewire        introducer needle (FIG. 3O). The further guidewire introducer        needle is removed from under the skin to leave the further guide        wire extending under the skin. The maximum transverse        cross-section of the further guide wire is at least sufficiently        smaller than the inner lumen dimensions of the further guidewire        introducer needle so that the further guide wire may be        inserted—in other words, the further guide wire has a maximum        transverse cross-section less than the minimum internal        transverse cross-section of the further guidewire introducer        needle. The length is at least the distance from the first        incision 1250 to the third incision 1270. Typically, a gauge of        20G is used; Preferably, the same guide wire 3040 is used as        described above in relation to FIG. 3K; and    -   a second introducer assembly 3060 a,b is inserted under the skin        over the further guidewire (FIG. 3P). The second introducer        assembly 3060 a,b comprises a second introducer sheath 3060 a        enclosing a hollow second introducer mandrin 3060 b. The lumen        of the second introducer mandrin 3060 b is at least large enough        to receive the further guide wire—in other words, the second        introducer sheath 3060 a has a minimum internal transverse        cross-section that is greater than the maximum transverse        cross-section of the further guide wire. The length is at least        the distance from the first incision 1250 to the third incision        1270. Typically, a gauge of 20G is used. The lumen of the second        introducer sheath 3060 a is also at least large enough to        receive the first portion 630 of the implantable stimulator 100,        102—in other words, the second introducer sheath 3060 a has a        minimum internal transverse cross-section that is greater than        the maximum transverse cross-section of the first portion 630 of        the stimulator. The method is particularly advantageous when the        second introducer sheath 3060 a has a maximum internal        transverse cross-section less than the maximum proximal        transverse cross-section 710 of the substrate 300. The second        introducer 3060 a,b may be identical, similar or different to        the first introducer 3050 a,b. It may the same type of        introducer, but with identical, similar or different dimensions.

In summary, the method comprises at least the steps of:

-   -   identifying a target location for stimulation;    -   forming a first 1250 and second 1260 incision on opposite sides        of the target location;    -   forming a third 1270 incision between the first 1250 and second        1260 incisions;    -   introducing the first introducer sheath 3050 a under the skin        from the second incision 1260 to the third incision 1270;    -   introducing a second introducer sheath 3060 a under the skin        from the third incision 1270 to the first incision 1250, the        first and second introducer sheaths 3050 a, 3060 a having        maximum internal transverse cross-section less than the maximum        proximal transverse cross-section 710 of the substrate 300;    -   introducing the first portion 630 of the implantable stimulator        100, comprising the at least two electrodes 200, 400, into the        second introducer sheath 3060 a from the first incision 1250 to        the third incision 1270;    -   removing the second introducer sheath 3060 a;    -   introducing the first portion 630 of the implantable stimulator        100, comprising the at least two electrodes 200, 400, into the        first introducer sheath 3050 a from the third incision 1270 to        the second incision 1260; and    -   removing the first introducer sheath 3050 a, whereby the        implantable stimulator extends under the skin from the further        portion 610 at the first incision 1250 to the first portion 630        at the second incision 1260.        whereby the at least two electrodes 200, 400 are arranged to        transfer treatment energy to the target location.

So, using a first and second introducer sheath 3050 a, 3060 a and threeincisions 1250, 1260, 1270, the stimulator 100, 101, 102, 103, 104, 105,may be implanted at many target locations in the body of the subjectwhere the further portion 610 and first portions 630 are to be implantedover at least one portion of curved skin.

The methods described above using one or more introducer sheaths may beused to reliably position a stimulation device at an implantation sitesufficiently close to the nerve to be stimulated. Additionally, themethods described below for reliably implanting under the nerve may beused to further improve the introducer sheath methods.

A further complication is determining a suitable subcutaneous depth forthe portion with at least two electrodes 200, 400.

FIG. 2A depicts a transverse cross-section through the head of a subject1000 in a median plane. In particular, it depicts in transversecross-section, the layers of skin typically found at the back 1015 ofthe subject's 1000 head in the target region for left occipital nerve830 b stimulation and/or right occipital 840 b nerve stimulation.Anatomical landmarks also depicted are the mastoid process 1050 and the(external) occipital protuberance inion 1035.

At this target location 830 b, 840 b for stimulation, superior (“above”)to the mastoid process 1050 and superior (“above”) to the occipitalprotuberance inion 1035, the skin comprises a plurality of layers,including (in order of increasing depth from outer to inner): an outerskin layer 2001, subcutaneous fat 2005 surrounding the nerve tissue 2003to be stimulated, an (inner) aponeurosis layer 2009 and underlying bonetissue 2015.

In more detail, the skin at this target location may include (in orderof increasing depth from outer to inner): an outer skin layer 2001,subcutaneous fat 2005 surrounding the nerve tissue 2003 to bestimulated, an (inner) aponeurosis layer 2009, a periosteum layer 2013and underlying bone tissue 2015.

In general, aponeurosis 2009 is a type or a variant of the deep fasciathat attaches sheet-like muscles needing a wide area of attachment.Their primary function is to join muscles and the body parts they actupon, whether bone or other muscles.

In general, fascia is a band or sheet of connective tissue, primarilycollagen, beneath the skin that attaches, stabilizes, encloses, andseparates muscles and other internal organs.

Skin layers may also include one or more layers of connective tissueand/or one or more layers of fascia. For clarity, these have not beenincluded in the drawings, and are not discussed in detail in thisapplication.

The implantation method therefore comprises:

-   -   forming one or more 1250, 1260, 1270 incisions proximate the        target location;    -   removing one or more skin layers, including an outer skin layer        2001 and subcutaneous fat 2005; and    -   introducing the first portion 630 in the skin whereby the at        least two electrodes 200, 400 are disposed between the nerve        tissue 2003 to be stimulated and the aponeurosis layer 2009. The        first portion 630 may be disposed above the aponeurosis layer        2009.

As the skin layers are removed one-by-one, it is relativelystraightforward for the specialist to identify the transition betweenthe subcutaneous fat layer 2005 and the underlying tissue, such as theaponeurosis layer 2009 and/or the periosteum layer 2013.

Aponeurosis 2009 appears to be shiny, with a whitish-silvery color. Thelayers 2009 are usually very sparingly supplied with blood vessels andnerves.

By introducing the first portion 630 below the subcutaneous fat layer2005 in a region with aponeurosis 2009, the chance that the firstportion 630 is implanted under the nerve tissue 2003 to be stimulated isvery high.

This has the advantage over other proposed locations for stimulatorimplantations. Conventionally, stimulators are often implanted in thesubcutaneous fat layer 2005 in locations 2050 closer but superior(“above”) to the mastoid process 1050. The mastoid process 1050 islocated posterior and inferior (“below”) to the ear canal, lateral tothe styloid process, and appears as a conical or pyramidal projection.These proposed locations 2050 are inferior (“below”) to the occipitalprotuberance inion 1035.

At this conventional location 2050, the skin comprises a differentplurality of layers (in order of increasing depth from outer to inner):an outer skin layer 2001, subcutaneous fat 2005, muscle tissue 2019surrounding the nerve tissue 2003 to be stimulated, a periosteum layer2013 and underlying bone tissue 2015.

A frequent disadvantage of such conventional locations 2050 is theextended distance to the nerve tissue to be stimulated, which typicallyrequires a higher level of energy to be transferred into tissue, whichmay reduce energy efficiency. This may also result in unwantedstimulation of muscle tissue 2019 disposed between the nerve 2003 andthe stimulator 2050.

Aponeurosis 2009 is mainly found at skin locations where there is littleor no muscle tissue 2019. So by selecting locations where aponeurosis2009 is present, the risk that muscle tissue 2019 is disposed betweenthe stimulator 101 and the nerve tissue 2003 to be stimulated is greatlyreduced.

In addition, the risk of unwanted muscle stimulation may be reduced dueto the reduced risk of being close to muscle tissue 2019.

It may be advantageous to introduce the first portion 630 such that theat least two electrodes 200, 400 is disposed in skin layers directlyadjacent to or in the aponeurosis layer 2009. There are fewer bloodvessels, so the risk of damage to other anatomical structures may alsobe reduced. For example:

-   -   between subcutaneous fat 2005 and the aponeurosis layer 2009;    -   directly adjacent to the aponeurosis layer 2009;    -   in the aponeurosis layer 2009.

It therefore reduces the risk even further that the first portion 630 isinserted over the nerve tissue 2003 to be stimulated. In this context,“under” the nerve 2003 is a skin depth location between the nerve tissue2003 and the underlying bone tissue 2015, and “over” the nerve 2003 is askin depth location between the nerve tissue 2003 and an outer skinlayer 2001.

By being implanted deeper, comfort for the subject may be improved. Inaddition, if it the chance that the stimulator is implanted under thenerve tissue is relatively high, it may allow a first portion withelectrodes on only one surface (either the first or second surface) tobe more reliably used.

It is advantageous to implant any type of stimulator with one or morestimulation electrodes under the occipital nerve tissue 2003 to bestimulated. Particularly advantageous is to implant the first portion630 of a stimulator as disclosed herein 100, 101, 102, 103, 104, 105under the nerve tissue 2003 to be stimulated. It is even moreadvantageous to use the method depicted in FIG. 8A to FIG. 8O anddescribed above.

By using a first portion 630 with a greatly reduced thickness, such as0.5 mm or less, introduction deeper under the skin becomes possible.Additionally or alternatively, comfort for the subject may be improvedif the stimulator 101 is located deeper under the skin.

By using a conformable first portion 630, insertion may be made moreprecisely at the interfaces between skin layers—the risk may be reducedof tissue damage during insertion, and the conformable first portion 630may more easily follow anatomical curvature.

FIG. 2B depicts a transverse cross-section through the head of a subject1000 in a median plane. In particular, it depicts in transversecross-section, the layers of skin typically found at the forehead 1010of a subject 1000 in the target region for left supraorbital nerve 810stimulation and/or right supraorbital 820 nerve stimulation.

At this target location 810, 820 for stimulation, superior (“above”) tothe orbita 1031, the skin comprises a plurality of layers, including (inorder of increasing depth from outer to inner): an outer skin layer2001, nerve tissue 2003 to be stimulated, an (inner) aponeurosis layer2009 and underlying bone tissue 2015.

In more detail, the skin at this target location may include (in orderof increasing depth from outer to inner): an outer skin layer 2001,subcutaneous fat 2005 surrounding the nerve tissue 2003 to bestimulated, an (inner) aponeurosis layer 2009, a periosteum layer 2013and underlying bone tissue 2015.

These are the same layers as described above for FIG. 2A, so theadvantages and disadvantages discussed are also the same.

The target locations 810, 820 have the advantage over other proposedlocations for stimulator implantations. Conventionally, stimulators areoften implanted in the subcutaneous fat layer 2005 in locations closer(less superior) to the orbita 1031.

At these conventional locations 2055, the skin comprises a differentplurality of layers (in order of increasing depth from outer to inner):an outer skin layer 2001, subcutaneous fat 2005, muscle tissue 2019surrounding the nerve tissue 2003 to be stimulated, a periosteum layer2013 and underlying bone tissue 2015.

These are the same layers as described above for FIG. 2A, so thedisadvantages discussed are also the same.

It is advantageous to implant any type of stimulator with one or morestimulation electrodes under the supraorbital nerve tissue 2003 to bestimulated. Particularly advantageous is to implant the first portion630 of a stimulator as disclosed herein 100, 101, 102, 103, 104, 105under the nerve tissue 2003 to be stimulated. It is even moreadvantageous to use the method depicted in FIG. 3A to FIG. 3V anddescribed above.

FIG. 2C depicts a transverse cross-section through the head of a subject1000 in a coronal plane. The coronal plane or frontal plane divides thehead into front and back parts.

In particular, it depicts in transverse cross-section, the layers ofskin typically found superior (“above”) to the right ear 1020 of asubject 1000 in a convenient region for the further portion 610 to beimplanted. In this example, it depicts a cross-section through the firstincision 1250 depicted in FIG. 3A to 3V.

At this convenient location, the skin comprises a plurality of layers,including (in order of increasing depth from outer to inner): an outerskin layer 2001, muscle tissue 2019, and underlying bone tissue 2015.

In more detail, the skin at this target location may include (in orderof increasing depth from outer to inner): an outer skin layer 2001, asubcutaneous fat layer 2005, muscle tissue 2019, a periosteum layer 2013and underlying bone tissue 2015.

These are similar layers as described above for FIG. 2A and FIG. 2B, sothe advantages and disadvantages discussed are also the same. At theselocations, muscle tissue 2019 is present, so there is little or noaponeurosis 2009. It is also preferably a region selected with little orno nerve tissue, so it is not necessary to take this into account whendetermining the implantation depth. In particular, insertion close tothe interface between the subcutaneous fat layer 2005 and the underlyingtissue layers 2019, 2013 generally requires less force to be applied.

The implantation method of the further portion 610 therefore comprises:

-   -   forming an incision 1250 proximate the implantation location;    -   removing one or more skin layers, including an outer skin layer        2001 and subcutaneous fat 2005; and    -   introducing the further portion 610 of the substrate 300 in the        skin layers, whereby the further portion 610 is disposed between        subcutaneous fat 2005 and above or in muscle tissue 2019.

This may allow a more complete implantation of the implantablestimulator, which may reduce infection risk, and may increase thepositional stability of the first portion 630.

As the skin layers are removed one-by-one, it is relativelystraightforward for the specialist to identify the transition betweenthe subcutaneous fat layer 2005 and the underlying tissue, such asmuscle tissue 2019 and/or the periosteum layer 2013.

Conventionally, implants are implanted just under the outer layer ofskin 2001. However, by implanting deep or below subcutaneous fat 2005,comfort may be improved for the subject as the further portion 610 iscovered by more skin layers. It may also be advantageous for thespecialist to implant the first portion 630 and further portion 610 atapproximately the same depth in the skin.

In embodiments where the further portion 610 is also implanted, it maybe advantageous for the further portion 610 to be disposed above or inthe muscle tissue 2019. For example:

-   -   between the subcutaneous fat layer 2005 and the aponeurosis        layer 2009;    -   adjacent to the muscle tissue 2019;    -   in the muscle tissue 2019.

Deeper locations may increase the amount of skin layers that cover thefurther portion 610, which may further increase comfort for the subject.

It is advantageous to implant any type of stimulator with a furtherportion directly adjacent or in muscle 2019. Particularly advantageousis to implant the further portion 610 of a stimulator as disclosedherein 100, 101, 102, 103, 104, 105. It is even more advantageous to usethe methods depicted in FIG. 3A to FIG. 3V or FIG. 8A to 8O, asdescribed above.

The methods described above may be used to reliably implant below thenerve tissue to be stimulated. Additionally, the methods described aboveusing one or more introducer sheaths may be used to further improve theunder-nerve implantation methods.

FIG. 5 and FIG. 6 depict examples of nerves that may be stimulated usinga suitably configured implantable first portion of stimulators 100, 101,102, 103, 104, 105 to provide neurostimulation to treat, for example,headaches or primary headaches.

FIG. 5 depicts the left supraorbital nerve 910 and right supraorbitalnerve 920 which may be electrically stimulated using a suitablyconfigured device. FIG. 6 depicts the left greater occipital nerve 930and right greater occipital nerve 940 which may also be electricallystimulated using a suitably configured device.

Depending on the size of the region to be stimulated and the dimensionsof the portions of the device to be implanted, a suitable location maybe determined to provide the electrical stimulation required for thetreatment. For example, one or more of:

-   -   if an appropriate location can be found to make the pocket for        the further portion 610, then the stimulator 100, 101, 102, 103,        104, 105, may be implanted using an introducer sheath 3050 a and        two incisions 1250, 1260;    -   if the specialist wishes to position the further portion further        away, or the region of skin is curved, then the stimulator 100,        101, 102, 103, 104, 105, using a first and second introducer        sheath 3050 a, 3060 a and three incisions 1250, 1260, 1270.

Approximate implant locations for the distal part of the stimulationdevice comprising stimulation devices 100, 101, 102, 103, 104, 105 aredepicted in FIG. 5 and FIG. 6 as regions:

-   -   location 810 for left supraorbital stimulation and location 820        for right supraorbital stimulation for treating chronic headache        such as migraine and cluster.    -   location 830 a or location 830 b for left occipital stimulation        and location 840 a or location 840 b for right occipital        stimulation for treating chronic headache such as migraine,        cluster, and occipital neuralgia.

In many cases, these will be the approximate locations 810, 820, 830a/b, 840 a/b for the implantable stimulator 100, 101, 102, 103, 104,105.

For each implant location, 810, 820, 830 a/b, 840 a/b a separatestimulation system may be used. Where implant locations 810, 820, 830a/b, 840 a/b are close together, or even overlapping, a singlestimulation system may be configured to stimulate at more than oneimplant location 810, 820, 830 a/b, 840 a/b by increasing the length ofthe substrate 300 and/or the length of the portion with at least twoelectrodes 200, 400.

A plurality of stimulation devices 100, 101, 102, 103, 104, 105 may beoperated separately, simultaneously, sequentially or any combinationthereof to provide the required treatment.

FIG. 7 depict further examples of nerves that may be stimulated using asuitably configured improved implantable stimulator 100, 101, 102, 103,104, 105 to provide neurostimulation to treat other conditions. Thelocations depicted in FIG. 5 and FIG. 6 (810, 820, 830, 840) are alsodepicted in FIG. 7.

Depending on the size of the region to be stimulated and the dimensionsof the part of the device to be implanted, a suitable location isdetermined to provide the electrical stimulation required for thetreatment. Approximate implant locations for the part of the stimulationdevice comprising stimulation electrodes are depicted as regions:

-   -   location 810 for cortical stimulation for treating epilepsy;    -   location 850 for deep brain stimulation for tremor control        treatment in Parkinson's disease patients; treating dystonia,        obesity, essential tremor, depression, epilepsy, obsessive        compulsive disorder, Alzheimer's, anxiety, bulimia, tinnitus,        traumatic brain injury, Tourette's, sleep disorders, autism,        bipolar; and stroke recovery    -   location 860 for vagus nerve stimulation for treating epilepsy,        depression, anxiety, bulimia, obesity, tinnitus, obsessive        compulsive disorder, heart failure, Crohn's disease and        rheumatoid arthritis;    -   location 860 for carotid artery or carotid sinus stimulation for        treating hypertension;    -   location 860 for hypoglossal & phrenic nerve stimulation for        treating sleep apnea;    -   location 865 for cerebral spinal cord stimulation for treating        chronic neck pain;    -   location 870 for peripheral nerve stimulation for treating limb        pain, migraines, extremity pain;    -   location 875 for spinal cord stimulation for treating chronic        lower back pain, angina, asthma, pain in general;    -   location 880 for gastric stimulation for treatment of obesity,        bulimia, interstitial cystitis;    -   location 885 for sacral & pudendal nerve stimulation for        treatment of interstitial cystitis;    -   location 885 for sacral nerve stimulation for treatment of        urinary incontinence, fecal incontinence;    -   location 890 for sacral neuromodulation for bladder control        treatment; and    -   location 895 for fibular nerve stimulation for treating gait or        footdrop.

Other condition that may be treated include gastro-esophageal refluxdisease, an autoimmune disorder, inflammatory bowel disease andinflammatory diseases.

Depending on the size of the region to be stimulated and the dimensionsof the portions of the device to be implanted, a suitable location maybe determined to provide the electrical stimulation required for thetreatment. For example, one or more of:

-   -   if an appropriate location can be found to make the pocket for        the further portion 610, then the stimulator 100, 101, 102, 103,        104, 105, may be implanted using an introducer sheath 3050 a and        two incisions 1250, 1260;    -   if the specialist wishes to position the further portion further        away, or the region of skin is curved, then the stimulator 100,        101, 102, 103, 104, 105, using a first and second introducer        sheath 3050 a, 3060 a and three incisions 1250, 1260, 1270.    -   in many cases, appropriate locations can also be found where the        at least two electrodes 200, 400 are disposed under the nerve        tissue 2003 to be stimulated and above or in the aponeurosis        layer 2009.

The conformability and minimum thickness of the substrate 100 andportion with at least two electrodes 200, 400 makes one or moreimplantable stimulators 100, 101, 102, 103, 104, 105 highly advantageousfor the stimulation of one or more nerves, one or more muscles, one ormore organs, spinal cord tissue, brain tissue, one or more corticalsurface regions, one or more sulci, and any combination thereof.

The descriptions thereof herein should not be understood to prescribe afixed order of performing the method steps described therein. Rather themethod steps may be performed in any order that is practicable.Similarly, the examples are used to explain the algorithm, and are notintended to represent the only implementations of these algorithms—theperson skilled in the art will be able to conceive many different waysto achieve the same functionality as provided by the embodimentsdescribed herein.

Many types of implantable first portions of stimulation devices aredepicted. But this does not exclude that the rest of the device isimplanted. This should be interpreted as meaning that at least theelectrode portion of the first portion is preferably configured andarranged to be implanted.

The invention is not limited to the particular embodiments illustratedin the drawings and described above in detail. Those skilled in the artwill recognize that other arrangements could be devised, for example:

-   -   one or more electrodes of the first type 200 a, 200 b are        comprised in the first surface 310 and one or more electrodes of        the second type 400 a, 400 b are comprised in the second surface        320; or    -   one or more electrodes of the first type 200 a, 200 b are        comprised in the first surface 310 and one or more electrodes of        the second type 400 a, 400 b are also comprised in the first        surface 310; or    -   one or more electrodes of the first type 200 a, 200 b are        comprised in the second surface 320 and one or more electrodes        of the second type 400 a, 400 b are comprised in the first        surface 310; or    -   one or more electrodes of the first type 200 a, 200 b are        comprised in the second surface 320 and one or more electrodes        of the second type 400 a, 400 b are also comprised in the second        surface 320; or    -   any combination thereof.

FIGS. 4A, 4B and 4C depict alternative portions with at least twoelectrodes 200, 400 configurations suitable for being comprised in animplantable stimulator 100, 101, 102 as described herein.

FIG. 4A depicts an implantable first portion of a further embodiment 103of a stimulator. Similar to the first portion depicted in FIG. 1C, thefirst surface 310 comprises:

-   -   two electrodes 200 a, 200 b of a first type and two electrodes        400 a, 400 b of a second type. From proximal to first portion,        the order depicted is 200 a, 400 a, 200 b, 400 b—in other words,        each electrode of the first type 200 a, 200 b is proximate an        electrode of the second type 400 a, 400 b and comprised in the        same surface 310.

The first portion depicted in FIG. 4A is the same as that depicted inFIG. 1A, except:

-   -   the electrodes 200, 400 are extended at angle to the        longitudinal axis 600. This may reduce the sensitivity to        longitudinal misalignment because the longitudinal locations        over which tissue stimulation may be provided are increased.

Additionally or alternatively, the second surface 320 may similarlycomprise two electrodes 200 a, 200 b of the first type and twoelectrodes 400 a, 400 b of the second type.

As discussed above, each electrode 200 a, 200 b, 400 a, 400 b may beoperated as one or more stimulation electrodes or operated as one ormore return electrodes.

FIG. 4B depicts an implantable first portion of a further embodiment 104of a stimulator. Similar to the first portion depicted in FIG. 1C, thefirst surface 310 comprises four electrodes. However, in this embodiment104, the first surface 310 comprises:

-   -   four electrodes 200 a, 200 b, 200 c, 200 d of a first type and        an electrode 400 of a second type. From proximal to first        portion, the order depicted is 200 a, 200 b, 200 c, 200 d.        Transversely adjacent to the four electrodes of the first type        200 is an electrode of the second type 400, extending        longitudinally to be adjacent to each electrode of the first        type 200.

Nominally, the electrodes of the first type 200 may be operated as oneor more stimulation electrodes. The electrode of the second type 400 maybe nominally operated as a return electrode for one or more of thestimulation electrodes.

This may reduce the sensitivity to longitudinal misalignment because thefour different longitudinal locations are provided which may be selectedfor stimulation over which tissue stimulation may be provided areincreased.

Additionally or alternatively, the second surface 320 may similarlycomprise four electrodes 200 a, 200 b, 200 c, 2003 of the first type andone adjacent and longitudinally extended electrode 400 of the secondtype.

As discussed above, each electrode 200 a, 200 b, 200 c, 200 d, 400 maybe operated as one or more stimulation electrodes or operated as one ormore return electrodes.

FIG. 4C depicts an implantable first portion of a further embodiment 105of a stimulator. Similar to the first portion depicted in FIG. 4B, thefirst surface 310 comprises four electrodes 200 a, 200 b, 200 c, 200 dof a first type. However, in this embodiment 105, the first surface 310further comprises four adjacent electrodes 400 a, 400 b, 400 c, 400 d ofa second type. From proximal to first portion, the order depicted is 200a/400 a, 200 b/400 b, 200 c/400 c, 200 d/400 d. Transversely adjacent toeach of the four electrodes of the first type 200 is an electrode of thesecond type 400 at approximately the same disposition along thelongitudinal axis 600.

Nominally, the electrodes of the first type 200 may be operated as oneor more stimulation electrodes. The electrodes of the second type 400may be nominally operated as a return electrode for one or more of thestimulation electrodes. Nominally, adjacent electrodes may be consideredas a stimulation/return pair 200/400.

In other words, a 2×4 electrode array is provided—two along a transverseaxis and four along the longitudinal axis.

This may reduce the sensitivity to longitudinal misalignment because thefour different stimulation/return 200/400 pairs are provided atsubstantially different longitudinal locations are provided which may beselected for stimulation over which tissue stimulation may be providedare increased.

Additionally or alternatively, the second surface 320 may similarlycomprise four electrodes 200 a, 200 b, 200 c, 200 d of the first typeand four adjacent electrodes 400 a, 400 b, 400 c, 400 d of the secondtype.

As discussed above, each electrode 200 a, 200 b, 200 c, 200 d, 400 a,400 b, 400 c, 400 d may be operated as one or more stimulationelectrodes or operated as one or more return electrodes. This may alsoreduce the sensitivity to a transverse misalignment.

The stimulator 100, 101, 102, 103, 104, 105 may further comprise:

-   -   an energy receiver, configured and arranged to wirelessly        receive energy from an associated energy transmitter when the        associated energy transmitter is proximate;        the pulse generator 500 being further configured and arranged to        receive electrical energy from the energy receiver for its        operation.

The stimulator 100, 101, 102, 103, 104, 105 may be further modified. Forexample:

-   -   the substrate 300 and pulse generator 500 may be embedded in one        or more flexible bio-compatible encapsulation layers. These        layers may comprise: a Liquid Crystal Polymer (LCP), a        Polydimethylsiloxane (PDMS), a silicone polyurethane, a        Polyimide, a parylene, a biocompatible polymer, a biocompatible        elastomer, and any combination thereof.

By providing relatively larger higher electrode 200, 400 surfaces,stimulators 100, 101, 102, 103, 104, 105 may be operated at a lowerenergy/lower power. This may be advantageous in applications where highfrequency and/or burst stimulation is used.

High frequency operation may require more energy to be provided by thepulse generator 500. In applications where energy/power is critical (forexample, if an increased operating lifetime is desired from a powersource for the pulse generator 500), any reduction in required power maybe advantageous. High frequency operation may be considered asgenerating electrical stimulation pulses with a frequency of 1000 Hz ormore, preferably 1500 Hz or more, more preferably 2000 Hz or more, yetmore preferably 2500 Hz or more.

Experiments with burst stimulation have been performed—for example,Burst Occipital Nerve Stimulation for Chronic Migraine and ChronicCluster Headache by Garcia-Ortega et al, Neuromodulation 2019; 22:638-644, DOI: 10.1111/ner.12977.

For burst operation, the pulse generator 500 is further configured andarranged to generate electrical stimulation pulses in groups ofstimulation pulses.

For example, groups (or bursts) of stimulation pulses may comprise 2 to10 pulses, more preferably 2 to 5 stimulation pulses. Stimulation pulsesin a group may have, for example, a repetition frequency of more than500 Hz, typically 1000 Hz or more. Groups may be repeated, for example,at more than 5 Hz, typically 40 Hz or more.

As with high frequency operations, burst operation may require moreenergy to be provided by the pulse generator 500, and any reduction inrequired power may be advantageous.

Additionally, the speed of charge-balance recovery may also increasewith a lower impedance. By using a relatively thin-foil substrate 300,stimulation between an electrode of the first type 200 comprised in onesurface 310, 320 and an electrode of the second type 400 comprised inthe other surface 310, 320, the current path in tissue is relativelyshort, reducing impedance.

Similarly, using a substrate 300, and stimulation between an electrodeof the first type 200 comprised in one surface 310, 320 and an adjacentelectrode of the second type 400 comprised in the same surface 310, 320,provide a relatively short path through tissue.

The invention encompasses every possible combination of the variousfeatures of each embodiment disclosed. One or more of the elementsdescribed herein with respect to various embodiments can be implementedin a more separated or integrated manner than explicitly described, oreven removed or rendered as inoperable in certain cases, as is useful inaccordance with a particular application While the invention has beendescribed with reference to specific illustrative embodiments,modifications and variations of the invention may be constructed withoutdeparting from the spirit and scope of the invention as set forth in thefollowing claims.

REFERENCE NUMERALS

-   100, 101, 102 implantable stimulators-   103, 104, 105 further embodiments of implantable stimulators-   200 a, 200 b one or more stimulation electrodes-   250 one or more stimulation electrical interconnection layers-   300 a substrate-   310 a first surface of the substrate-   320 a second surface of the substrate-   350 a portion of the substrate comprising no stimulation electrodes-   400 a, 400 b one or more return electrodes-   500 a pulse generator-   600 a longitudinal axis-   610 a further portion or a proximal end-   630 a first portion or a distal end-   700 a first transverse axis-   710 a maximum proximal transverse cross-section-   730 a maximum distal transverse cross-section-   750 a second transverse axis-   800 median plane of subject-   810 location for left supraorbital nerve or cortical stimulation-   820 location for right supraorbital nerve or cortical stimulation-   830 a first location for left occipital nerve stimulation-   830 b second location for left occipital nerve stimulation-   840 a first location for right occipital nerve stimulation-   840 b second location for right occipital nerve stimulation-   850 location for deep brain stimulation-   860 location for vagus nerve, carotid artery, carotid sinus, phrenic    nerve or hypoglossal stimulation-   865 location for cerebral spinal cord stimulation-   870 location for peripheral nerve stimulation-   875 location for spinal cord stimulation-   880 location for gastric stimulation-   885 location for sacral & pudendal nerve stimulation-   890 location for sacral neuromodulation-   895 location for fibular nerve stimulation-   910 left supraorbital nerve-   920 right supraorbital nerve-   930 left greater occipital nerve-   940 right greater occipital nerve-   1000 subject being treated-   1010 forehead of subject-   1015 back of subject's head-   1020 right ear of subject-   1021 left ear of subject-   1030 right orbita of subject-   1031 left orbita of subject-   1035 occipital protuberance inion-   1040 vascular structure-   1050 mastoid process-   1100 (optional) area to be shaved-   1200 extent for portion with at least two electrodes—(b) left to (a)    right-   1210 extent for further portion—(b) left to (a) right-   1220 offset from landmark-   1250 a first incision-   1260 a second incision-   1270 a third incision-   2001 outer skin layer-   2003 nerve tissue-   2005 subcutaneous fat-   2009 aponeurosis layer-   2013 periosteum layer-   2015 bone tissue, for example skull-   2019 muscle tissue-   2050 typical location for occipital nerve stimulation-   2055 conventional location for supraorbital nerve stimulation-   3000 tissue marker-   3010 tissue knife, e.g. a surgical scalpel-   3020 blunt scissors/forceps-   3030 a,b guidewire introducer needle assembly (a, b) comprising a    guidewire introducer needle (a) and a removable guidewire introducer    mandrin (b)-   3040 guide wire-   3050 a,b first introducer assembly (a, b) comprising a first    introducer sheath (a) and a removable first introducer mandrin (b)-   3060 a,b second introducer assembly (a, b) comprising a second    introducer sheath (a) and a removable second introducer mandrin (b)-   3070 tweezers, such as silicone-tipped tweezers

The invention claimed is:
 1. A method for implanting an implantablestimulator under nerve tissue of a subject, the implantable stimulatorcomprising: a substrate, comprising a first surface and a secondsurface, wherein a thickness of the substrate is defined by the firstand second surfaces; and at least two electrodes, located along aconformable first portion of the substrate, the thickness of thesubstrate along the conformable first portion being equal to or lessthan 0.5 millimeters; the method comprising: identifying a targetlocation for stimulation which in transverse cross-section comprises anouter skin layer, nerve tissue to be stimulated, and an inneraponeurosis layer; forming one or more incisions proximate the targetlocation; introducing the conformable first portion in the skin layersat the target location, whereby the at least two electrodes are disposed(a) under the nerve tissue to be stimulated and (b) above or in theinner aponeurosis layer.
 2. The method according to claim 1, the methodfurther comprising: introducing the conformable first portion, wherebythe at least two electrodes are disposed in the skin layers betweensubcutaneous fat and the aponeurosis layer.
 3. The method according toclaim 1, the method further comprising: introducing the first portion,whereby the at least two electrodes are disposed in the skin layersdirectly adjacent to the aponeurosis layer.
 4. The method according toclaim 1, the method further comprising: removing one or more skinlayers, including an outer skin layer and subcutaneous fat, beforeintroducing the first portion.
 5. The method according to claim 1, themethod further comprising: forming an incision proximate an implantationlocation; and introducing a further portion of the substrate in the skinlayers via the incision proximate an implantation location, whereby thefurther portion is disposed below at least some subcutaneous fat andabove or in muscle tissue.
 6. The method according to claim 5, themethod further comprising: introducing the further portion, whereby thefurther portion is disposed in the skin layers between subcutaneous fatand a bone layer.
 7. The method according to claim 5, the method furthercomprising: introducing the further portion, whereby the further portionis disposed in the skin layers directly adjacent to the muscle tissue.8. The method according to claim 5, the method further comprising:removing one or more skin layers, including an outer skin layer andsubcutaneous fat, before introducing the further portion.
 9. The methodaccording to claim 5, the implantable stimulator further comprising apulse energy receiver or pulse generator located along the furtherportion.
 10. The method according to claim 5, wherein the thickness ofthe substrate along the further portion is 4 millimeters or less. 11.The method according to claim 1, wherein: the substrate islongitudinally-extended, further comprising a further portion; and thefirst portion has a first maximum transverse cross-section and thefurther portion has a further maximum transverse cross-section, thefurther maximum transverse cross-section being at least 1.2 times thefirst maximum transverse cross-section; the one or more incisionsproximate the target location a first incision and a second incision onopposite sides of the target location; the method further comprising:introducing a first introducer sheath under the skin from the secondincision to the first incision, the first introducer sheath having amaximum internal transverse cross-section less than the further maximumtransverse cross-section of the substrate; introducing the conformablefirst portion, comprising the at least two electrodes, into the firstintroducer sheath from the first incision to the second incision;removing the first introducer sheath, whereby the implantable stimulatorextends under the skin from the further portion at the first incision tothe conformable first portion at the second incision, whereby the atleast two electrodes are arranged to transfer treatment energy to thetarget location.
 12. The method according to claim 11, the methodfurther comprising: forming a third incision between the first andsecond incisions; introducing the first introducer sheath under the skinfrom the second incision to the third incision instead of from thesecond incision to the first incision; introducing a second introducersheath under the skin from the third incision to the first incision, thesecond introducer sheath having a maximum internal transversecross-section less than the further maximum transverse cross-section ofthe substrate; introducing the first portion of the implantablestimulator, comprising the at least two electrodes, into the secondintroducer sheath from the first incision to the third incisionposition; removing the second introducer sheath; introducing the firstportion of the implantable stimulator, comprising the at least twoelectrodes, into the first introducer sheath from the third incision tothe second incision; and removing the first introducer sheath, wherebythe implantable stimulator extends under the skin from the furtherportion at the first incision to the first portion at the secondincision.
 13. The method according to claim 1, wherein the substratecomprises a first and second surface defining a thickness of thesubstrate, the thickness of the substrate along the conformable firstportion being 0.3 millimeter or less.
 14. The method according to claim1, wherein the conformable first portion is foil-like, comprising two ormore adjacent polymeric substrate layers.
 15. The method according toclaim 1, wherein the conformable portion comprises a Liquid CrystalPolymer (LCP).
 16. The method according to claim 1, wherein thesubstrate comprises a first conformable layer and at least one secondconformable layer, wherein a plurality of electrical interconnectionlayers are positioned along the first layer using a depositiontechnique, and wherein the at least one second layer is secured to thefirst layer so as to cover the plurality of electrical interconnections.17. The method according to claim 1, the method further comprisingconfiguring and arranging the implantable stimulator for stimulating:one or more nerves, one or more muscles, one or more organs, spinal cordtissue, brain tissue, one or more cortical surface regions, one or moresulci, and any combination thereof.
 18. The method according to claim 1,the method further comprising configuring and arranging the implantablestimulator for treatment of: headaches, primary headaches, incontinence,occipital neuralgia, sleep apnea, hypertension, gastro-esophageal refluxdisease, an inflammatory disease, limb pain, leg pain, back pain, lowerback pain, phantom pain, chronic pain, epilepsy, an overactive bladder,poststroke pain, obesity, an autoimmune disorder, rheumatoid arthritis,inflammatory bowel disease, Crohn's disease, and any combinationthereof.
 19. A method for implanting an implantable stimulator, theimplantable stimulator comprising: a longitudinally-extended substratehaving a conformable first portion and a further portion; at least twoelectrodes, comprised in the conformable first portion; wherein thefirst portion has a first maximum transverse cross-section and thefurther portion has a further maximum transverse cross-section, thefurther maximum transverse cross-section being at least 1.2 times thefirst maximum transverse cross-section; the method comprising:identifying a target location of a subject for stimulation; forming afirst and second incision on opposite sides of the target location;introducing a first introducer sheath under the skin from the secondincision to the first incision, the first introducer sheath having amaximum internal transverse cross-section less than the further maximumtransverse cross-section of the substrate; introducing the conformablefirst portion, comprising the at least two electrodes, into the firstintroducer sheath from the first incision to the second incision;removing the first introducer sheath, whereby the implantable stimulatorextends under the skin from the further portion at the first incision tothe conformable first portion at the second incision whereby the atleast two electrodes are arranged to transfer treatment energy to thetarget location.
 20. The method according to claim 19, the methodfurther comprising: introducing a guide wire under the skin between thefirst and second incisions, the guide wire having a maximum transversecross-section less than the minimum internal transverse cross-section ofthe introducer sheath; introducing the first introducer sheath over theguide wire under the skin from the second incision to the firstincision; and removing the guidewire, whereby the first introducersheath extends under the skin from the second incision to the firstincision.
 21. The method according to claim 19, the method furthercomprising: inserting the tip of an guidewire introducer needle into thefirst incision and further inserting the guidewire introducer needleunder the skin until the tip emerges from the second incision, theguidewire introducer needle having a minimum internal transversecross-section greater than the maximum transverse cross-section of theguide wire; inserting the guide wire through the guidewire introducerneedle; and removing the guidewire introducer needle from under the skinto leave the guide wire extending under the skin through the firstincision to the second incision.
 22. The method according to claim 19,the method further comprising: forming a skin pocket around the firstincision, arranged to accept the further portion of the implantablestimulator; and introducing the further portion of the implantablestimulator into the skin pocket at the first incision.
 23. The methodaccording to claim 19, wherein the target location is under nerve tissueof the subject.
 24. The method according to claim 19, wherein theimplantable stimulator further comprises a pulse energy receiver orpulse generator located along the further portion.
 25. The methodaccording to claim 19, wherein the substrate comprises a first andsecond surface defining a thickness of the substrate, the thickness ofthe substrate along the further portion is 5 millimeters or less,preferably 4 millimeters or less, even more preferably 3 millimeters orless.
 26. The method according to claim 19, the method furthercomprising: forming a third incision between the first and secondincisions; introducing the first introducer sheath under the skin fromthe second incision to the third incision instead of from the secondincision to the first incision; introducing a second introducer sheathunder the skin from the third incision to the first incision, the secondintroducer sheath having a maximum internal transverse cross-sectionless than the further maximum transverse cross-section of the substrate;introducing the first portion of the implantable stimulator, comprisingthe at least two electrodes, into the second introducer sheath from thefirst incision to the third incision position; removing the secondintroducer sheath; introducing the first portion of the implantablestimulator, comprising the at least two electrodes, into the firstintroducer sheath from the third incision to the second incision; andremoving the first introducer sheath, whereby the implantable stimulatorextends under the skin from the further portion at the first incision tothe first portion at the second incision.
 27. The method according toclaim 19, wherein the target location identified for stimulationcomprises, in transverse cross-section, an outer skin layer, nervetissue to be stimulated, and an inner aponeurosis layer; the methodfurther comprising: introducing the conformable first portion in theskin layers at the target location, whereby the at least two electrodesare disposed under the nerve tissue to be stimulated and above or in theaponeurosis layer.
 28. A method for implanting an implantable stimulatorunder nerve tissue of a subject, the implantable stimulator comprising:a substrate, comprising a first surface and a second surface, wherein athickness of the substrate is defined by the first and second surfaces;at least two electrodes, located along a conformable first portion ofthe substrate, the thickness of the substrate along the conformablefirst portion being equal to or less than 0.3 millimeters; wherein thesubstrate is longitudinally-extended, further comprising a furtherportion; and a pulse energy receiver or pulse generator located alongthe further portion; wherein the thickness of the substrate along thefurther portion is 4 millimeters or less; wherein the conformable firstportion has a first maximum transverse cross-section and the furtherportion has a further maximum transverse cross-section, the furthermaximum transverse cross-section being at least 1.2 times the firstmaximum transverse cross-section; wherein the conformable first portionis foil-like, comprising two or more adjacent polymeric substratelayers; wherein the conformable first portion comprises a Liquid CrystalPolymer (LCP); wherein a plurality of electrical interconnection layersare positioned along a first of the polymeric substrate layers using adeposition technique, and wherein at least one second of the polymericsubstrate layers is secured to the first layer so as to cover theplurality of electrical interconnections; the method comprising:identifying a target location for stimulation which in transversecross-section comprises an outer skin layer, nerve tissue to bestimulated, and an inner aponeurosis layer; forming a first incision anda second incision on opposite sides of the target location; introducinga first introducer sheath under the skin from the second incision to thefirst incision, the first introducer sheath having a maximum internaltransverse cross-section less than the further maximum transversecross-section of the substrate; forming another incision in line withand outside the first and second incisions; introducing a secondintroducer sheath under the skin from the first incision to the anotherincision, the second introducer sheath having a maximum internaltransverse cross-section less than the further maximum transversecross-section of the substrate; introducing the conformable firstportion of the implantable stimulator, comprising the at least twoelectrodes, into the second introducer sheath from the another incisionto the first incision; removing the second introducer sheath;introducing the conformable first portion of the implantable stimulator,comprising the at least two electrodes, into the first introducer sheathfrom the first incision to the second incision; and removing the firstintroducer sheath, whereby the implantable stimulator extends under theskin from the further portion at the another incision to a tip of theconformable first portion at the second incision, whereby the at leasttwo electrodes are arranged under the nerve tissue to be stimulated andbetween subcutaneous fat and the aponeurosis layer, directly adjacent tothe aponeurosis layer; removing one or more skin layers, including anouter skin layer and subcutaneous fat, before introducing theconformable first portion; forming an incision proximate an implantationlocation; introducing the further portion of the substrate in the skinlayers via the incision proximate the implantation location, whereby thefurther portion is disposed below at least some subcutaneous fat,directly adjacent to and above or in muscle tissue, and betweensubcutaneous fat and a bone layer; removing one or more skin layers,including an outer skin layer and subcutaneous fat, before introducingthe further portion; and configuring and arranging the implantablestimulator for stimulating one or more nerves for treatment ofheadaches.